Last month, researchers announced some astonishing findings in Nature Genetics: Theyd found 40 genes that play a role in shaping human intelligence, bringing the total number of known intelligence genes up to 52.

This study was a big deal because while weve known intelligence is largely heritable, we havent understood the specifics of the biology of IQ why it can be so different between people, and why we can lose it near the end of life.

The Nature Genetics study was a key early step toward understanding this, hailed as an enormous success in the New York Times.

And there are many more insights like this to come. The researchers used a design called a genome-wide association study. In it, computers comb through enormous data sets of human genomes to find variations among them that point to disease or traits like intelligence. As more people have their genomes sequenced, and as computers become more sophisticated at seeking out patterns in data, these types of studies will proliferate.

But theres also a deep uneasiness at the heart of this research it is easily misused by people who want to make claims about racial superiority and differences between groups. Such concerns prompted Nature to run an editorial stressing that the new science of genetics and intelligence comes to no such conclusions. Environment is crucial, too, Nature emphasized. The existence of genes for intelligence would not imply that education is wasted on people without those genes. Geneticists burned down that straw man long ago.

Also, nothing in this work suggests there are genetic difference in intelligence when comparing people of different ancestries. If anything, it suggests that the genetics that give rise to IQ are more subtle and intricate than we can ever really understand.

Were going to keep getting better at mapping the genes that make us smart, make us sick, or even make us lose our hair. But old fears and myths about genetics and determinism will rear their heads. So will fears about mapping ideal human genes that will lead to designer babies, where parents can pick traits for their children la carte.

To walk through the science, and to bust its myths, I spoke to Danielle Posthuma, a statistical geneticist at Vrije Universiteit in Amsterdam, who was the senior author on the latest Nature study.

Theres a simple understanding of genetics were all taught in high school. We learn, as Gregor Mendel discovered with pea plants, that we can inherit multiple forms of the same gene. One variation of the gene makes wrinkled peas; the other makes for round peas. Its true, but its hardly the whole story.

In humans, a few traits and illnesses work like this. Whether the bottom of your earlobes stick to the side of your face or hang free is the result of one gene. Huntingtons disease which deteriorates nerve cells in the brain is the result of a single gene.

But most of the traits that make you you your height, your personality, your intellect arise out of a complex constellation of genes. There might be 1,000 genes that influence intelligence, for example. Same goes for the genes that lead to certain disorders. Theres no one gene for schizophrenia, for obesity, for depression.

A single gene for one of these things also wont have an appreciable impact on behavior. If you have the bad variant of one gene for IQ, maybe your IQ score ... is 0.001 percent lower than it would have been, Posthuma says.

But if you have 100 bad variants, or 1,000, then that might make a meaningful difference.

Genome-wide association studies allow scientists to start to see how combinations of many, many genes interact in complicated ways. And it takes huge data sets to sort through all the genetic noise and find variants that truly make a difference on traits like intelligence.

The researchers had one: the UK Biobank, a library that contains genetic, health, and behavioral information on 500,000 Britons. For the study, they pulled complete genome information on 78,000 individuals who had also undergone intelligence testing. Then a computer program combed through millions of sites on the gene code where people tend to variate from one another, and singled out the areas that correlated with smarts.

The computer processing power needed for this kind of research this study had to crunch 9.3 million DNA letters from 78,000 people hasnt been available very long. But now that it is, researchers have been starting to piece together the puzzle that links genes to behaviors.

A recent genome-wide analysis effort identified 250 gene sites that predicted male pattern baldness in a sample of 52,000 men. (Would you really want to know if you had them?) And theres been progress identifying genes that signal risk for diabetes, schizophrenia, and depression.

And these studies dont just look at traits, diseases, and behavior. Theyre also starting to analyze genetic associations to life outcomes. A 2016 paper in Nature reported on 74 gene sites that correlate with educational attainment. (These genes, the study authors note, seem to have something to do with the formation of neurons.) Again, these associations are tiny the study found that these 74 gene variants could only explain 3 percent of the difference between any two people on what level of education they achieve. Its hardly set in stone that youll flunk school if you dont have these gene variants.

But still, they make a small significant difference once you start looking at huge numbers of people.

Its important to note that Posthumas study was only on people of European ancestry. Whatever we find for Europeans doesnt necessarily [extrapolate] for Asians or South Americans, [or any other group] she says. Those things are often misused.

Which is to say: The gene variations that produce the differences between Europeans arent necessarily the same variations that produce differences among groups of different ancestry. So if you were to test the DNA of someone of African origin, and saw they lacked these genes, it would be incredibly irresponsible to conclude they had a lower capacity for intelligence. (Again, there are also likely hundreds of more genetic sites that have something to do with intellect that have yet to be discovered.)

Posthumas work identifying genes associated with intelligence isnt about making predictions about how smart a baby might grow up to be. She doesnt think you can reliably predict educational or intelligence outcomes from DNA alone. This is all really about reverse-engineering the biology of intelligence.

Genes code for proteins. Proteins then interact with other proteins. Researchers can trace this pathway all the way up to the level of behavior. And somewhere along that path, there just might be a place where we can intervene and stop age-related cognitive decline, for instance, and Alzheimers.

We're finally starting to see robust reliable associations from genes with their behavior, she says. The next step is how do we prove that this gene is actually evolved in a disorder, and how does it work?

Understanding the biology of intelligence could also lead the way for personalized approaches to treating neurodegenerative diseases. Its possible that two people with Alzheimers may have different underlying genetic causes. Knowing which genes are causing the disease, then, you might be able to tailor the treatment, Posthuma says.

As more and more genome-wide studies are conducted, the more researchers will be able to assign people polygenic risk scores for how susceptible they might be for certain traits and diseases. That can lead to early interventions. (Or, perhaps in the wrong hands, a cruel and unfair sorting of society. Have you seen the movie Gattaca?)

And there are some worries about abusing this data, especially as more and more people get their genomes analyzed by commercial companies like 23&Me.

Many people are concerned that insurance companies will use it, she says. That the
y will look into people's DNA and say, Well, you have a very high risk of being a nicotine addict. So we want you to pay more. Or, You have a high risk of dying early from cancer. So you have to pay more early in life. And of course, that's all nonsense. Its still too complicated to make such precise predictions.

We now have powerful tools to edit genes. CRISPR/Cas9 makes it possible to cut out any specific gene and replace it with another. Genetic engineering has advanced to the point where scientists are building whole organisms from the ground up with custom DNA.

Its easy to indulge our imaginations here: Genome-wide studies are going to make it easier to predict what set of genes leads to certain life outcomes. Genetic engineering is making it easier to assemble whatever genes we want in an individual. Is this the perfect recipe for designer babies?

Posthuma urges caution here, and says this conclusion is far afield from the actual state of the research.

Lets say you wanted to design a human with superior intelligence. Could you just select the right variants of the 52 intelligence genes, and wham-o, we have our next Einstein?

No. Genetics is so, so much more complicated than that.

For one, there could be thousands of genes that influence intelligence that have yet to be discovered. And they interact with each other in unpredictable ways. A gene that increases your smarts could also increase your risk for schizophrenia. Or change some other trait slightly. There are trade-offs and feedback loops everywhere you look in the genome.

If you would have to start constructing a human being from scratch, and you would have to build in all these little effects, I think we wouldn't be able to do that, Posthuma says. It's very difficult to understand the dynamics.

There are about 20,000 human genes, made up of around 3 billion base pairs. We will never be able to fully predict how a person will turn out based on the DNA, she says. Its just too intricate, too complicated, and also influenced heavily by our environment.

So you could have a very high liability for depression, but it will only happen if you go through a divorce, she says. And who can predict that?

And, Posthuma cautions, there are some things that genome-wide studies cant do. They cant, for instance, find very, very rare gene variations. (Think about it: If one person in 50,000 has a gene that causes a disease, its just going to look like noise.) For schizophrenia, she says, we know that there's some [gene] variants that decrease or increase your risk of schizophrenia 20-fold, but they're very rare in the population.

And they cant be used to make generalizations about differences between large groups of people.

Last year, I interviewed Paul Glimcher, a New York University social scientist whose research floored me. Glimcher plans to recruit 10,000 New Yorkers and track everything about them for decades. Everything: full genome data, medical records, diet, credit card transactions, physical activity, personality test scores, you name it. The idea, he says, is to create a dense, longitudinal database of human life that machine learning programs can mine for insights. Its possible this approach will elucidate the complex interactions of genetics, behavior, and environment that put us at risk for diseases like Alzheimers.

Computer science and biology are converging to make these audacious projects easier. And to some degree, the results of these projects may help us align our genes and our environments for optimal well-being.

Again, Posthuma cautions: Not all the predictions this research makes will be meaningful.

Do we care if we find a gene that only increases our height or our BMI or our intelligence with less than 0.0001 percent? she asks. It doesn't have any clinical relevance. But it will aid our scientific understanding of how intellect arises nonetheless.

And thats the bottom line. The scientists doing this work arent in it to become fortune tellers. Theyre in it to understand basic science.

What most people focus on, when they hear about genes for IQ, they say: Oh, no. You can look at my DNA. You can tell me what my IQ score will be, Posthuma says. They probably dont know its much better if you just take the IQ test. Much faster.

See the original post here:
Scientists are finding more genes linked to IQ. This doesn't mean we can predict intelligence. - Vox

Diamondback moths. (Credit: Oxitec)

Though genetically modified crops may steal the spotlight, similarly reprogrammed insects may have just as big an effect on the agricultural industry.

Biotechnology company Oxitec is moving forward withplans to develop genetically engineered diamondback moths in an attempt to reduce populations of the invasive crop pest. Their plan is to release males that will pass on a gene preventing female offspring from reaching maturity and reproducing, which they say will eventually eradicate the moths in North America. Tests have so far been positive, although there are still worries about the prospect of releasing genetically modified organisms into the wild.

Currently, pesticides are used to control the moths, which are responsible for an estimated $5 billion worth of damage every year in the U.S. An invasive species, the diamondback moth originated in Europe, but has proved difficult to control since appearing the U.S. due to short gestation times and the large numbers of eggs females lay at once. Oxitec says that their technique is preferable to pesticides, as the moths have proven capable of evolving resistance to the compounds in the past, and most carry some risk to the environment and human health.

Oxitec cites a USDAanalysis that found no risk of significant impact in an earlier test of the GM moths as evidence that their technique is safe, but the prospect of GM insects raisesfears that the moths may proliferate beyond targeted areasand cause impacts on the broader ecology. Similar techniques have been applied before, reaching as far back as the 1950s when sterile screwworm flies were released in Florida, effectively eliminating the parasitic species there. Impotent mosquitos, also manufactured by Oxitec, have been used to combat Zika in South America, andplans to implement the same procedure in Florida are underway.

The successful screwworm campaign relied on blasts of radiation to sterilize the males. Oxitecs technique uses gene editing engineering to implant males with modified DNA that ensures female caterpillars dont survive to adulthood. In the case of the moths, males need not be targeted because it is only the female caterpillars who are responsible for damaging the crops.

They say that tests of the moths, including feeding them to various animals and releasing them in greenhouses, have revealed no ill effects as a result of the genetic modification. Along with the caterpillar-killing gene, the moths are also implanted with a gene that causes them to fluoresce red under UV light, the better to identify them in the wild.

The FDA found no issues preventing the company from moving forward, but because the moths are an agricultural pest, the USDA must weigh in as well.Oxitec is currently waiting on USDA approval to conduct expanded tests at a site in New York in conjunction with Cornell University. They hope to release the moths in a contained cabbage field to see how effective their modifications are.

Most opposition to genetically modified insects is based on the prospect of altered organisms spreading beyond the areas they are released. In the case of the diamondback moth, Oxitec says that the nature of the modification, which precludes breeding, should serve to limit the spread of the GM moths, and pesticides and freezing winter conditions should take care of the rest. While there is a precedent for this kind of technique in screwworms, those insects were uniquely suited to sterilization-based population control because of their life-cycles. Moths may present additional challenges.

Kevin Esvelt, a professor at MIT and leader of the Sculpting Evolution Lab agrees that the general concept is sound: The wholepoint is to harm the next generation of organisms. And since they carry the relevant genetic construct, its necessarily going to decrease, he says. It will not persistin the environment over time as long as the genetic construct is doing what its supposed to do.

This marks a crucial difference from a gene drive, a technique often associated with genetically modifying populations. The hallmark of a gene drive is tweaking genes to increase the chances that a particular trait will be passed on to offspring. The odds are normally 50/50, but a gene drive can tilt them in favor of a particular set of genes,causing a trait to spread through a population. This is helpful when a trait is detrimental to an organisms survival and would normally be weeded out by natural selection. Gene drives havent yet been applied in the wild, though, and likely wont be for many years.

Oxitecs moths possess nosuch scale-tipping modifications that could cause the modified genes to spread across the globe, they merely pass on genetic material in the normal way. Part of this genetic material, however, has been changed to ensure that female caterpillars with the gene dont survive.

From a technical perspective its a perfectly sound approach, it probably offers fewer risks than current approaches using pesticides. In general I am a fan of usingbiology to solve ecological problems as opposed to chemistry, Esvelt says.

Still, he says that field trials are an important step in testing the efficacy and safety of any genetically modified organism. Along with careful tests, Esvelt advocates for more community involvement in the decision making process, as well attempts to reach out and communicate with critics. Although both the FDA and USDA have a period in place during which the public can comment, Esvelt says more communication should be done earlier.

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After Mosquitos, Moths Are the Next Target For Genetic Engineering - Discover Magazine (blog)

Picture this: The year is 2167, and climate change has caused temperatures to rise to a level so high that the human race can longer sustain itself.

That's part of the premise behindGenetic Drift,an immersive theatre production produced by Boca del Lupo and created by Jesse Richardson-award winning Pi Theatre.

Built on the speculative fiction concept introduced by Boca del Lupo and the Performance Corporation's Expedition Series,Genetic Driftanswers the question, "how will climate change affect the world 150 years in the future?"

Pi Theatre's artistic director, Richard Wolfe, was tasked with coming up with an answer to that question.

"I thought, possibly, in the face of climate change, were going to have to adapt to something quite extreme," he said in an interview with the Straightat Boca del Lupo's micro performance space on Granville Island.

"Hows that going to happen? Well, perhaps through genetic engineering, because just recently, with CRISPR technology, they are now able to remove and splice in DNA from other places into human embryos," he added.

For Wolfe and writer Amy Lee Lavoie, this meant introducing a character from the future.

Played by Thomas Jones, Gary 3 is a human/creature hybrid who has been forcibly kidnapped from the future and brought to modern times for the viewing pleasure of audience members.

"The role is challenging in that it's not an entirely human character, so getting your head and your body around how this creature with some other DNA spliced into it actually physically moves and communicates was difficult," said Jones. "That, and also to imagine what his perspective is when being confronted with people like us, today."

For Keltie Forsythe, who plays the voice of Lucy the computer,the technology that's responsible for bringing Gary to present day, Genetic Driftoffers viewers a chance not to watch a show, but to really experience it.

"We hope [the audience] will be sucked in by Garyhe's a charming guy," she says. "We hope that they'll feel some things around Gary,and what hes going through 150 years into the future as this kind of genetically-engineered creature, and the kind of alienation he feels."

Curious about how Boca del Lupo and Pi Theatre made it happen? Check out an exclusive preview ofGenetic Driftin the video below.

Genetic Driftplays at Boca del Lupo's Fishbowl on Granville Island from April 5 to 8. Find tickets here.

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In Genetic Drift, mutant humans are the answer to surviving extreme ... - Straight.com

Each year, fungal infections destroy at least 125 million tons of the world's five most important crops -rice, wheat, maize, soybeans and potatoes- a quantity that could feed 600 million people. Fungi are not only a problem in the field, but also produce large losses in the post-harvest stage: during product storage, transport or in the consumer hands. Also, it should be noted that some fungi produce mycotoxins, substances capable of causing disease and death in both humans and animals. Farmers use fungicides to treat fungal infections, but these are not always 100% effective and, moreover, consumer demands pesticide-free products.

Like humans, plants have developed defense strategies to protect themselves against pathogen attacks. Now a team from the Centre for Research in Agricultural Genomics (CRAG), in Spain, has found that the regulation of the protein activity in the plant by the mechanism known as SUMOylation is crucial for the plant protection against fungal infections.

The study, which has just been published in the specialized journal Molecular Plant, is the result of a collaboration between two CSIC researchers at CRAG: Maria Lois, expert in protein regulation, and Mara Coca, expert in plant immune responses to pathogen infection. As Maria Lois explains, "the results of this research will be used to develop new strategies for crop protection against fungal infection."

SUMOylation: difficult to study but essential for living organisms

SUMO protein binding to other cellular proteins (SUMOylation) is a key process for many cellular functions. For example, in animals, some cancers and neurodegenerative diseases are associated to a defective SUMOylation. In plants, it is known that SUMO conjugation regulates plant development and their responses to environmental stresses.

However, until now SUMOylation roles have been difficult to study because, its complete inhibition causes plant death at the seed stage. To overcome these limitations, Maria Lois' research group has developed a new tool to inhibit the SUMOylation only partially, so the plant can develop normally. Using genetic engineering techniques, the CRAG researchers introduced in the plant a small protein fragment that partially inhibits the SUMOylation.

Plants more susceptible to fungal infections

Using this new approach, CRAG's team found that plants with compromised SUMOylation showed an increased susceptibility to necrotrophic fungal infections by Botrytis cinerea and Plectosphaerella cucumerina. "These two fungi cause plant death and feed on dead tissues. Botrytis cinerea is a geographically widespread fungus which infects many species of plants. It is well known for viticulturists because it produces both the noble rot and the grey rot in wine grapes, affecting the wine quality. Plectosphaerella cucumerina is a model of study, but is also an important pathogen of vegetable crops such as melon" explains the CSIC researcher at CRAG, Maria Coca.

In addition, the researchers observed that shortly after the fungal infection, protein SUMOylation was decreased in the infected plants. This observation suggested that the necrotrophic fungi reduce protein SUMOylation as a mechanism of pathogenicity. Thus, this study opens new opportunities for developing novel strategies for crop protection against pathogenic fungi, as well as for the development of more specific fungicides

A new strategy useful for plants and animals

The strategy designed by Maria Lois' team to partially inhibit the SUMOylation has been key in this study, but it is expected that its applications will go much further. "This new approach will allow us to better understand SUMOylation-regulated processes and, most importantly, it is a tool that can be easily implemented in agronomically important plants, even in those with high genetic complexity, such as wheat," explains Lois. "We believe that there are still many important SUMOylation functions to discover, and we have designed a molecular tool that will be helpful in this regard," the researcher adds.

Indeed, Maria Lois has already taken steps for transferring the knowledge gained from her plant SUMOylation studies to the field of human health. These activities have been supported by the European Research Council (ERC) and by the Government of Catalonia through the respective programs and Proof-of-Concept and Llavor.

Read more here:
Key mechanism in the plant defense against fungal infections - Science Daily

Dr. Luhan Yang, chief scientific officer at eGenesis, says she wants to pay back to society with her work in genetic engineering.

CAMBRIDGE Where other people see bacon, biologist Luhan Yang sees lifesaving organs hundreds and thousands of them, pig livers and pig kidneys and diabetes-curing pancreases, and possibly hearts and lungs, all growing inside droves of pampered swine.

More established scientists than Yang have dreamed of creating animal organs that are suitable for transplantation into people waiting for a human donor. But until recently, experts said it would take decades to genetically alter pig organs to make them work safely in people. Most dreamers gave up.

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Giving up is not in Yangs lexicon. Urgency is. In her native China, she told STAT, 2 million people need organ transplants, and people are dying before they get one.

The intensely driven 31-year-old has a few things going for her that other would-be pioneers did not. As a Harvard graduate student, Yang was a lead author of a breakthrough 2013 study on the genome-editing technology CRISPR-Cas9. And in 2015, she cofounded the biotech company eGenesis with her mentor, legendary Harvard bioengineer George Church, with whom shes also worked on trying to resurrect the Ice Age wooly mammoth through genetic legerdemain. From eGenesiss tiny headquarters in Kendall Square, she intends to use CRISPR to accomplish what the worlds largest drug companies failed to do despite investing billions of dollars: create designer pigs whose organs can be transplanted into people.

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Luhan is a remarkable person, Church said, and a force of nature.

She better be. Daunting hurdles stand between where biology is now and where it needs to be to make transplantable pig organs. The old problems of infection and rejection of another species organs seem almost quaint compared to those facing eGenesis.

Theres the challenge of CRISPRing an unprecedented number of genes without compromising the viability of the designer pigs and without introducing aberrant edits. And of optimizing mammalian cloning, which is how the company creates the pigs. And of persuading investors and doctors that xenotransplantation, as the process is called, is safe, effective, ethical and lucrative.

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Yang, eGenesiss chief scientific officer, has already made enormous strides, both scientific and financial. In 2015, she and colleagues in Churchs lab used CRISPR to eliminate from pig cells 62 genes so potentially dangerous their very existence nixed previous efforts to turn pigs into organ donors. Last month, eGenesis announced that it had raised $38 million from investors. The next hurdle: get the surrogate-mother sows that are pregnant with genetically altered embryos to give birth to healthy piglets.

Her work has the potential to change the face of transplantation and to save countless lives, said Dr. James Markmann, chief of transplant surgery at Massachusetts General Hospital.

Yang is not only confident of success, she also sees eGenesiss xeno work as a sort of trial run for even bolder goals. In 2016, she helped conceive Genome Project-write, whose aims include assembling a synthetic human genome from off-the-shelf parts and because, really, as long as youre making a human genome, why not? doing it better than nature.

By starting from scratch, she wonders, could we make the human genome cancer-resistant? ... Or make it virus-resistant? ... There is a great opportunity that xeno can tell us what would happen in humans after dramatic genome engineering.

But if eGenesis is to succeed in making designer pigs, let alone paving the way for new and improved humans, Yang will need to fix the miscarriage problem.

On a frigid March morning, Yang is holding her monthly meeting with Church and the companys half-dozen employees, getting updates on the designer-pig pipeline and lighting a fire under her team. The big conference table in the windowless basement room is strewn with 8.5-ounce cans of Wild Jujube Drink and snacks that Yang brought back from her Lunar New Year visit to China, where she spent five days with her parents and visited eGenesiss pig colony.

The highlight of the month, biologist Marc Guell tells Yang, is that surrogate mother pigs didnt reinfect fetuses with PERVs. Thats crucial, because the memorably named infectious agents, short for porcine endogenous retroviruses, could cause tumors, leukemia, and neuronal degeneration if transplanted into patients. To make xenotransplantation succeed, PERVs have to go.

PERV genes are interwoven into the genome of pig cells, so eGenesis scientists start their work with CRISPR-Cas9, which has made editing organisms genomes so simple high-schoolers can do it. It takes far more expertise, however, to remove dozens of PERV genes at once, as eGenesis does in pig fibroblasts, which are connective-tissue cells.

EGenesis ships batches of these cells to China, where each de-PERVed pig cell is fused with a pig ovum whose own DNA has been removed. The ova, which now contain only the PERV-free genome, start dividing and multiplying, beginning the journey to becoming pig fetuses. The embryos are implanted into surrogate mothers and, if all goes well, born 114 days later. (Yang wont say how many sows are or have been pregnant.) Unfortunately, all has not gone well.

The anti-PERV work is only the start of the changes eGenesis is making to pig genomes. Its scientists are also slipping into the pig ova up to 12 human genes to make the pig organs more human-like, Yang said in an interview. One gene, she said, would shield its organs from attack by the human immune system; another would revamp its coagulation system to reduce the risk of clots.

Thats a ton of genetic handiwork for one little pig to handle, and early signs are it might be too much.

One batch of embryos all died, Yang said, possibly because their chromosomes had gotten scrambled by either the genetic changes or the lab manipulations. Another batch had a lot of miscarriage, she said.

There are other concerns, scientists noted at the March meeting. Sometimes PERVs are found in the embryos before theyre implanted into surrogate mothers. The problem, Yang says as she leaps to the front of the conference room, is that removing the DNA-containing nuclei from pig ova isnt always complete; occasionally some of an ovums own PERV-infested genes remain behind, so the embryo created from it also has PERVs, genetic analyses showed.

Yang grills her team. How prevalent is this? May I see the genetic profile again? What can we do quickly to correct the protocol? A gene that was inserted to protect other genes is the problem, she says with finality. Maybe we should pause this one and look for other solutions. Its better to figure out where the problem comes from, then we dont have the problem anymore.

A clue to how Yangs mind works is that she counts. Ask her about the ethical issues around xenotransplantation and she will immediately tell you there are three, then elaborate on them. Ask her what characteristics make up the entrepreneurial spirit and she will say there are four, then reel them off. Colleagues say she has an uncanny knack for working backward from an ultimate goal and breaking it into a manageable sequence of steps.

She darts down corridors, speaks quickly, hates waiting, and expects others to move at her speed. Some colleagues call her impatient. Biologist Dong Niu, who worked in the Church lab and is now at eGenesis, joined Yang on a recent blitz of apartment hunting. Yang set such a breakneck pace, Niu said, I couldnt even watch.

She pushes colleagues to accomplish tasks now, if not sooner, and when she asks a coworker to explain a scientific detail, she says, Were short of time; just get to the point.

Yet colleagues sing her prais
es, saying she motivates them and brings extraordinary passion and a laser focus to her work. Whenever you have a question, she has an answer, almost before you get it out, said Niu.

Yang was born and grew up in a small town in a mountainous region of southwest China. Her parents were ordinary working-class people, she said, her father a government employee and her mother an accountant.

In 2004, as a high school senior, she was chosen for Chinas four-person team in the 15th International Biology Olympiad, held in Australia. Yang was one of 16 contestants to win a gold medal, coming in 13th.

After majoring in psychology at Peking University, Yang entered graduate school at Harvard, where she rotated through three labs before joining Churchs. It was a crash course not only in biological engineering but also in what success means.

I think my generation of Chinese, we are very aggressive and very optimistic, Yang said. Sometimes I think we all want to be successful and to find a shortcut to be successful, because the competition [for academic success in China] is so fierce.

The different worldviews and value systems she saw at Harvard, she said, made me open my eyes and reassess what kind of person I want to be. I want to pay back to society.

Yang stumbled out of the gate in Churchs lab, nearly failing her PhD qualifying exams because her English was so poor. It was her first academic setback, but in relating the story, Yang betrayed no more emotion over the experience than if it had been another gene she had to CRISPR. George asked the committee to let me pass with the condition that he would spend more time with me for English training, Yang said.

She played point on some of the labs most important experiments. In 2012, she and postdoctoral fellow Prashant Mali teamed up on CRISPR-Cas9, a molecular complex that bacteria use as a primitive immune system; other scientists had recently gotten it to cut specific locations on DNA floating in test tubes. Mali and Yang got a single cluster of CRISPR molecules to edit multiple genes in human and mouse cells in one fell swoop, a breakthrough published in early 2013. Although Mali and Yang had equal billing as first authors, the paper is always referred to as Mali et al. Yang said that doesnt bother her.

Soon after, physicians approached Church about using CRISPR to alter the genomes of pigs so their organs would not be rejected by the human immune system. The very question was a triumph of hope over experience. In the 1990s, a handful of drug companies, including Novartis, had collectively spent north of $2 billion to use genetic manipulation to make human-friendly pig organs.

She said she feels a strong sense of responsibility to help the millions waiting for organs in her homeland: I regard myself as a Chinese scientist. Something that can potentially solve a huge health care and social problem for China and for the world? I feel it is a privilege to work on that.

With hundreds of labs catching CRISPR fever since 2013, most experiments have altered one or two genes at a time, maxing out at five. Yangs challenge was audacious: To knock out all the PERVs would require a tenfold improvement.

But if we could make it work, she said, the impact would be huge.

They did, and it has been. In 2015 the Church lab announced it had CRISPRd out 62 PERV genes in pig kidney cells growing in lab dishes. It was a record, and it still stands.

George always encouraged me to think bigger, Yang said.

Determined as she is to make xenotransplantation succeed, Yang also sees it as opening a back door for me to push the limit of [genomic] technology. For one thing, xenotransplantation requires large-scale genome engineering, she said. In addition to knocking out PERVs, which is relatively easy, making organ-donor pigs requires inserting large chunks of human DNA into the pig genome.

Our ability to knock in a large fragment of DNA is still limited, Yang said.

Working out how to do it in the pigs would point the way toward, say, adding copies of the cancer-fighting gene p53 into a persons genome.

Thats why I love xeno, she said. Its a platform to help us assess technology.

Yang has immersed herself in the ethical issues around xenotransplantation, but they havent slowed her pursuit of transplantable pig organs.

Some scholars argue that it is morally wrong to value human life more than animals, but so many people are eating pork every day, Yang said. As for playing God the argument that it is unethical to change a pig in the way that genome-editing does she retorts that the highest moral standard is human life. I think its a personal choice whether you use a pig organ or die. But you shouldnt prevent other people from using it.

As of early March, two of eGenesiss cloned and CRISPRd pig fetuses were just a few weeks from delivery, Yang said. We checked the genotype and were surprised but also delighted to see that the fetuses [in one surrogate mother] are 100 percent PERV-free.

Yang is more than ready to be a proud mother: I feel its our time.

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Cambridge company is making designer pigs with transplantable (to people) organs. - The Boston Globe

The tech world has embraced Machine Learning (ML) for its powerful intuitive capabilitiesto increase click-through rates on ads, sell more books, and help you keep in touch with mom. Despite being increasingly common as a classification tool in applications ranging from transcriptomics, metabolomics, and neuronal synaptic activities, ML is still almost absent in the area of bioengineering. Why is that and what can we do to increase ML use in bioengineering?

Machine Learning algorithms that date back half a century are now commonly used for pattern-based analysis, including Decision Trees, Nearest Neighbors, Neural Nets, and more recently with significant success Deep Learninga version of Neural Net with more layers and more nodesreceived significant attention when it won against the best human in the ancient Chinese game of Go. Deep Learning has been enabled by access to new powerful computational hardware, in particular the graphical processing units (GPUs) originally developed for the gaming industry. These gaming GPUs allow for massively parallel computations, which is perfect for ML applications. Its comforting to know that Call of Duty brought something of value to this world. In recent years we have seen ML flourishing in a broad range of applications where there is sufficient amounts of data to digest and classify; from self-driving cars to Barcelona FC soccer strategy, to deciding if you get the bank loan.

But think instead about a common diabetes complication, diabetic retinopathy, which results in irreversible blindness if not caught early. There are today >400 million diabetic patients at risk, many in underserved areas with limited access to clinical diagnosis. In a recent JAMA publication, Google Research applied Deep Learning to diagnose diabetic retinopathy patients from photographs of their retina. An initial set of 128,000 retina images was analyzed and scored by trained ophthalmologists for signs of onset of diabetic retinopathy. The images and the scoring were then processed by Googles Deep Learning software to identify patterns in the images that correlated with the clinical scoring. The resulting algorithm was subsequently validated with a separate set of ~12,000 images that the software had not seen before.

Not only did the Deep Learning image analysis software recognize early signs of the disease just as well as the human experts, it did so much more consistently. Its easy to see a day in the not too distant future when anyone with a smartphone will be able to diagnose this disease accurately and save millions of people from going blind. It will be exciting to see how fast this and similar algorithms will transform medical image based diagnosis in the areas of radiology, pathology, and dermatology.

Small molecule drug discovery is another arena where ML is rapidly gaining traction. Companies ranging from GSK and Pfizer to Atomwise, Numerate, and InSilico Medicine are compiling large datasets of ligands, targets, and associated biological functions to identify and quantify the patterns of ligand-target interactions using Deep Learning. Atomwise has an undisclosed, previously approved drug candidate that blocks Ebola infection as well as another promising lead molecule to treat multiple sclerosis. Both were identified using Deep Learning to find patterns among thousands (in the case of Ebola) and millions (in the case of multiple sclerosis) of related molecules and their physicochemical properties.

So if we understand the powerful and intuitive nature of ML, what has limited its application in bioengineering?

Is it just too new an idea? Probably not, seeing as early as the 1990s, thought leaders like David Haussler at UCSC and Tim Hunkapiller at Caltech were publishing papers using hidden Markov models to capture patterns in DNA and protein datasets. These patterns have subsequently propagated into PFAM and other well-established databases to classify enzymes from protein sequences. So its not a new idea.

Is it because we lack sufficiently large datasets? Maybe. Most curated sequence datasets that include quantified biological function are tiny (in the hundreds) and nonsystematic in that variables are rarely tested in more than one context. On the other hand, Genbank and WGS today encompass ~2 x1012 bp of naturally existing biological sequences and are growing very rapidly. This enormous dataset is however inherently highly correlated because of its evolutionary origin, making it difficult to separate causality from correlation and thus limiting its use for identifying sequence-function relationships. Also, only a vanishingly small part of the data is associated with quantified biological function. Despite these limitations, the Genbank and WGS datasets are extremely informative for e.g. protein engineering as they can readily be used to tell us where not to go. Sequences, elements, or amino acid combinations that never or rarely occurred in biology below some statistical threshold can be assumed to not fold and to not generate new biological functions.

Is it because of differing philosophy of science? Thats part of it. Machine Learning is based on inductive reasoning, i.e. pattern recognition. The system learns from making many observations and finding patterns that can be generalized to a conclusion/hypothesis. Contrary to the inductive reasoning so abundantly and so successfully used by tech companies such as Google, biotechnology has historically been a discovery-based research field led by deductive reasoning. In deductive reasoning we start from a theory and make predictions about what the corresponding observations should be if the theory is correct. Then we look for those observations. However, biology is a gooey and redundant complex megadimensional mess of synergy and antagonism, and an abundance of variables that just came along for the 4 billion year ride of evolution. It quickly becomes humanly impossible to build complex hypotheses that explain biological observation in accordance with deductive reasoning. This instead is the type of data that inductive ML thrives on.

Is it because the cost of making specific observations? Yes and No. The medicinal chemist assessing structure-activity relationships has to independently make and characterize each molecule in the dataset at a large cost. There is thus a significant incentive for the chemist to design and test molecules as efficiently as possible using all available toolsincluding MLto ensure success. This is in stark contrast to the molecular biologist who can make large semi-random datasets through methods like error-prone PCR or DNA shuffling at basically no cost. These gene libraries at sizes of 107-109 can be screened for e.g. binding using phage display or similar high-throughput procedures. Accordingly, the cost of finding a binder is small, diminishing the perceived need for tools such as ML. However, finding a binder is still a long way from making a protein pharmaceutical.

Biotechnology is implicitly well set up for ML applications. Contrary to medicinal chemistry and image-based diagnosis, there are a defined number of available options at each residue and any sequence can be made and tested for function. If we can complement our historical dependence on deductive reasoning with the inductive inference from ML, and increasingly look at biology as something to be engineered instead of a discovery-based science, ML has a bright future in bioengineering.

After all, if we can see our way to a future where ML and a smart phone can diagnose anyone for diabetes-induced blindness, why not use the same methodology perfected over click-through ads and playing Go to make improved antibodies, better vaccines, and novel diagnostic sensors?

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Building Biology with Machine Learning - Genetic Engineering & Biotechnology News

The goalposts of embryo ethics have shifted. Just two years ago, a Chinese study testing whether CRISPR-Cas9 genome editing could be used to cure beta thalassemia in human embryos was getting negative critiques. As quoted by Gina Kolata in a New York Times last June, a comment by Nobel laureate and former Caltech president David Baltimore illustrates the magnitude of the criticism:

[The study] shows how immature the science is. We have learned a lot from their attempts, mainly about what can go wrong.

Despite the criticism and disappointing results, its noteworthy that the researchers were careful to destroy all the embryos before they reached a gestational age of 14 days. Doing otherwise would have created an ethical dilemma, because going beyond 14 days would have taken the work outside of guidelines in place in all countries where such research is technically possible. Butchange may be in sight. Last week, Harvard genetic engineering pioneer George Church and colleagues published a thoughtful paper in eLife, Addressing the ethical issues raised by synthetic human entities with embryo-like features. Its a lengthy discussion, but the take-home message is that may betime to discardthe so-called 14-day rule.

As the Chinese researchers themselves pointed out, only a fraction of the embryos ended up with the genetic payload in their cells, so the technique was not adequately efficient. Furthermore, there was mosaicism: In several embryos that did get modified genetically, the change showed up in somecells, but not others. In other words, some embryonic cells were of the original, thalassemia genotype and the remainder were corrected. There also were off-target effects unintentional changes in other parts of the genome. All of this illustrated the potential danger of editing an entire organism, and germline editing, what is sometimes called heritable gene therapy changing genetic sequences that can be passed down to new generations. This meant that CRISPR, in its current form, was not reliable for correcting genetic diseases during pregnancy.

But none of this means the research should not have been conducted. For safety, the researches used human embryos that were not viable; they contained extra chromosomes, so it was not possible for them to develop into actual people. And of course, the team followed the rule about the 14 days.

As we shall see later, there is nothing magical about the 14-day mark in human embryology. But virtually every country with biotechnology advanced enough to maintain embryos outside the body has guidelines dictating that embryo research must not continue to gastrulation. This is the point when a blastula, consisting of a single layer of identical cells, reorganizes into a gastrula, consisting of three layers of cells, each of which will become a different kind of tissue. Gastrulation starts on day 15 with the appearance of whats called the primitive streak. This is the beginning of a head-to-tail orientation and over the past four decades some have given it a kind of moral status. This didnt matter much to science through the 1980s and 90s, because there was no technical capability to maintain human embryos in the lab more than a few days beyond fertilization. But things have changed. Today, researchers can maintain embryos right up through 14 days in Petri dishes. Its only on account of laws and guidelines that they dont go further. But doing socould have benefits, both for science and medicine. The question is whether things might change, now that ahigh profile genetics researcher has come forward advocating amore nuanced approach, rather thana simple cut-off point.

There is no scientific or cultural basis for giving moral status to gastrulation, and so the 14-day mark isan arbitrary point. The rule traces its birth to1979, when a board commissioned by the US Department of Health, Education, and Welfare soughta compromise position between scientists and social conservatives.

Soon after that, it was recognized that twinning splitting an embryo into two or more clones could produce a viable pregnancy only if it occurred before the primitive streak appeared. This presents a conflict for those religious people concerned with the issue of ensoulment the point at which asoul is believed to enter embryo. What happens to the soul of an embryo that splits into twins is relevant on to somebody who believes that ensoulment occurs in the early phase of development. However, religions that worry about souls dont dont align on the matter pertaining to embryos. In Islam, ensoulment occurs fairly late pregnancy, 120 days gestation being a commonly cited point. In Hinduism, the soul moves around between different animals, so there is no worry about it being created and split. Various Christians disagree on the timing of ensoulment, and in Judaism there is no talk of souls or ensoulment in connection to human development.

On top of this, there are vast numbers of purely secular-minded people throughout the world, for whom the embryo ethics is less about rights of potential human beings and more about the potential of embryo-based research to create new treatments for disease that make people suffer. Nevertheless, the main idea of the 1979 guideline has spread throughout the developed world, where current restrictions on embryo research vary from country to country, but still use gastrulation as the cut-off point.

The new paper by Church and his colleagues at Harvard and the University of Groningen calls for a nuanced discussion. They talk about special individual stem cells calledsynthetic human entities with embryo-like features (SHEEFs) available to researchers that can generate the same developmental features that are attributed to a developing embryo. They think this should be the basis of future regulations. In their words:

Our proposal to base research limits for SHEEFs directly on signifying features is based on the inference that, given the engineering methods used to create SHEEFs and their potential for developmental plasticity, revising limits in this way will be the only workable way to prevent the creation of SHEEFs in morally concerning conditions. But non-synthetic embryos go through the PS stage routinely and are not generally developmentally plastic in this way, so this conclusion does not follow. A more secure conclusion would be that, if for independent reasons the revision of the 14-day rule for embryos is justified, the considerations we have outlined for SHEEFs might be relevant to what new limit might replace it.

It already has people arguing in the comments section, and that discussion is expanding. On the Scientific American blog, for example, journalist Karen Weintraub quotes a handful of people from a range of perspectives, including Rev. Tadeusz Pacholczyk, a neuroscientist and director of education at the National Catholic Bioethics Center in Philadelphia:

Now were getting into experiments that call into question some of our deepest beliefs philosophically about what it means to be human and what it means to deserve moral respect.

What will happen if guidelines are relaxed? As explained in a New York Times OpEd piece last June, even discussing this will start a debate that pits scientists against religiously motivated people, which in this case means mostly fundamentalist Christians:

This technological advance has reopened the ethical debate about the 14-day limit. Many scientists chafe at restrictions on their ability to learn more about life and potentially create breakthrough therapies. Critics, especially religious believers, are horrified because they believe that, in the words of Philippa Taylor, head of public policy at the Christian Medical Fellowship, all embryos are very young human beings.

As discussed in the last section, the belief that embryos are people is limited to Christianity, which must be placed in context of a diverse society that includes more liberal Christians, as well as Jews, Muslims, people of eastern religions, and mill
ions of non-religious people. But if the history of stem cell policy and abortion serve as models, we can expect plenty of sanctimony and arguments rooted in questionable assumptions that the extreme Christian view represents some kind of universal ethics.

In the UK, where the first in vitro fertilization baby was born in 1978, the 14-day limit is more than a guideline. Rather, it is a strict rule, but since January it has been in the spotlight. In contrast with George Church, a handful of researchers are calling for a simple pushing back of the limit from 14 days to 28 days.

Now lets consider the long-term. Unlike in 1979, scientists today have the technical means to study embryos well into the period when different tissues and organs are forming, with potential science and medical benefits. Such benefits could come in the form of new treatments in regenerative medicine, since researchers could observe the precise genetics, cell biology, and chemistry of specific tissue and organ genesis. Progress toward an artificial womb. also would be accelerated. Furthermore, such studies could reveal the molecular biology underlying pregnancy loss through spontaneous abortion. Often these events are labeled as miscarriages, but many occur at very early gestational ages, before the woman even knows that she is pregnant. Thus, ironically, research on human embryos could end up saving future embryos from what happens when nature runs its course.

David Warmflash is an astrobiologist, physician and science writer. Follow @CosmicEvolution to read what he is saying on Twitter.

For more background on the Genetic Literacy Project, read GLP on Wikipedia.

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Time to amend human embryo research '14-day rule'? - Genetic Literacy Project

European Pharmaceutical Review explores how plants can be used for large-scale, glycosylated protein bioproduction for the pharma industry.

Plants can be used to produce large quantities of complex proteins, particularly glycosylated proteins, which are becoming more widely used in a range of therapies. Monoclonal antibodies (mAbs) are among the types of glycosylated proteins that plants can produce, but while there are multiple benefits to their use as bioreactors, there are also some key considerations.

This article explores why and how plants can be used to produce proteins for use in therapies, but also the factors that show this method may not be applicable to all protein products.

For plants to produce synthetic proteins, they must first be expressed somewhere within their genome. This requires some form of recombinant protein expression or genetic engineering, and to achieve optimum yield just implanting the gene is insufficient. To achieve a high level of transcription, which allows for downstream translation and protein modification for stability, the regulatory gene elements including the promoter and polyadenylation site must also be expressed.1

Techniques for gene expression:

There are three commonly used types of expression mechanisms for plant bioproduction: nuclear, chloroplast and transient expression.

Nuclear expression involves genetically modifying the genome in the nuclei of plants cells to express a protein. This is the simplest and most widely used approach in the pharmaceutical industry, as it can be achieved with viral vectors, but a more modern technique is CRISPR-Cas9 technologies.1 A 2018 study showed that in cotton, CRISPR showed no offtarget editing and an editing efficiency of 66.7 to 100 percent at each of multiple sites.2 The nuclear expression techniques, although reliable, are becoming less popular as they typically require more time to develop.

The second method involves expression of a recombinant protein in the chloroplasts requires a particle gun to insert the transgene. There are several benefits to this technique, including the ease of manipulating the chloroplast genome compared with the nucleus and the number of chloroplasts per cell, which increases yield. Using a transgene cassette to precisely target and insert the foreign gene avoids placing it into a poorly transcribed part of the genome, ensuring a high level of expression and little chance of silencing. Transgenes are commonly integrated between the trnltrnA genes in the rrn operon, as this is a transcriptionally active region offering high levels of gene expression.1

The third mechanism, transient expression, is becoming more common as it allows the rapid insertion of proteins, with little time required for the production, modification and optimisation of the expression system. Some companies have begun marketing this kind of expression for the rapid, large-scale production of proteins for therapeutics. The Agrobacteriummediated transient expression technique is purported to have better efficiency than the integrated gene systems and the ability to reach a high percentage of cells in a treated tissue, resulting in higher yields.1

In prokaryotic cells, like Escherichia coli (E. coli), protein size is limited to less than 30 kilodaltons, mainly due to reliability of production and yield. However, in eukaryotic cells, eg, Chinese hamster ovary (CHO) andplant cells, it is easier to produce larger proteins with high yields.1

According to experts, when using cell line or bacterial production methods such as CHO cells and E. coli to produce proteins, once the initial cell line is created it is often difficult to scale up, as glycosylation profiles become variable.3 The inconsistencies in protein product both cost money and result in waste.

On the other hand, dependent on expression mechanisms, plants can reliably maintain the glycosylation profile required even as bioreactor volume increases.

As a result of consistent production capabilities, plants do not require scale-up protocols. This saves both time and money when setting up a bioreactor.

A further advantage is that, if the plant is made to generate the protein through a transient expression system, there is very little time required to set up a production system. One company claims their tobacco plant-based system can be tailored for large-scale fabrication of a protein product in under 12 months, compared to 20-22 months with CHO or E. coli, 3 and one study suggests this could be done in a matter of weeks.1

There are multiple options for plant expression systems, particularly with regards to species, and each is best suited to produce different proteins. Genetic engineering can also be employed to allow customised N-glycosylation to generate different target products.

The plant industry is well established, with conditions for growth often being less complex than that of cell lines or bacteria and, dependent on choice of plant species, cultivation costs can be further reduced.

A techno-economic analysis of the theoretical set-up of a new large-scale biomanufacturing facility, producing mAbs using tobacco plants, found that compared to CHO production platforms, the plant system resulted in significantly reduced capital investment. Moreover, the model calculated that there would be more than a 50 percent reduction in the cost of goods, compared with published values for similar products at this production scale.4

One company has paved the way for the creation of biobetters, using their FastGlycaneering Development Service. iBio has shown that certain methods of plant bioproduction can improve the potency and homogeneity of biological medicines and ensure fully humanised glycosylation patterns.

iBio have also stated that their system, due to its consistencies in upstream processing, is compatible with artificial intelligence (AI). The company aim to implement a new end-to-end manufacturing process using AI and blockchain to reduce costs through optimising both the process and workflows.3

Some of the major challenges include regulatory approval, environmental contamination, protein stability and the immunogenicity of non-human post-translational modifications.1

Environmental concerns are predominantly from the possibility of spreading genetic modifications to food crops through pollination. This is more of a concern with the nuclear expression systems than transient or chloroplast expression. However, this can be overcome with geographical or physical containment, using a less transferable genetic modification method or through using a self-pollenating species.1

A review suggested that companies are unlikely to go through the cost of a shift from an already approved production system to seek regulatory approval for a new one.1 While altering an approved process is often unfeasible, setting up systems for the production of new products in the pipeline could prove to be more cost effective in the long run. Another consideration is the rising need for quick, large-scale vaccine production in response to pandemics and epidemics such as the Covid-19 coronavirus and Ebola which, due to the speed at which a transient expression production system can be constructed, could encourage companies to branch into this type of production.

Protein stability is a concern, as plants have endogenous enzymes that can break down the protein products. Some methods to overcome this include changing plant species and co-expressing peptides to fuse and stabilise the produced proteins together.

Post-translational modifications such as Asparagine-linked glycosylation (N-glycosylation) are one of the key worries, as they can be immunogenic. Particularly likely to cause unfavourable side effects are N-glycan modifications, because they differ in plants and humans.

N-glycosylation is a post-translational modification conducted on many secreted or membrane proteins in plants and mammals. Endogenously, it enables protein folding, stabilisatio
n and protein-protein interactions. It is similarly used in pharmaceutical bioproduction to stabilise products and provide antibodies and other proteins the correct pharmacokinetic properties and immunogenicity.5,6

The plant industry is well established, with conditions for growth often being less complex than that of cell lines or bacteria

While early N-glycosylation and N-glycan modifications are highly conserved between yeast, mammals and plants, later N-glycan modifications differ; they are more simplified in plants than mammals.5,6 So, to use plants as producers of fully humanised proteins, the plant glycosylation machinery is often removed and replaced with human machinery when the plant is modified to express the protein. Of note, chloroplasts have no glycosylation machinery, so cannot perform these modifications without the insertion of foreign DNA; although this can reduce immunogenicity of the products, it can limit which proteins can be produced by chloroplast expression.

Tobacco is the most widely used plant for production of recombinant proteins in the lab. High yield and rapid scale-up, due to large numbers of seeds produced, are the primary benefits. However, proteins stored in the leaves are vulnerable to degradation and must be stored or extracted appropriately, in a timely manner. Tobacco tissues can also contain phenols and toxic alkaloids that must be removed in downstream processing to make products safe.1

Cereals are primarily used due to their seed protein storage capabilities; cereal seeds have protein storage vesicles and a dry intracellular environment. Once dried, the seeds can be stored at room temperature with limited degradation to protein products or loss of activity. Use of food crops is particularly attractive as they offer the opportunity to administer oral vaccines produced in the crop by feeding them to patients with minimal processing. Some edible vaccines have reached Phase I trials.1

Peas are a particularly attractive option, as they have high protein content in their seeds similar to cereals and have lower nitrogen requirements, reducing cultivation costs. However, legumes usually have less leaf biomass than tobacco, meaning they require a larger area to produce the same quantity.1

Plants can be modified through several methods to express proteins and the requisite promoters and transcription controllers, for the production of therapeutic proteins. There are several important considerations, including protein expression methods and plant species; however, the many benefits, including reduced costs, adaptability and speed associated with plant bioproduction systems make them an attractive option.

A particular driver of this bioproduction process is the possibility of using transient expression to produce vast quantities of highly potent, fully humanised vaccines in response to pandemics and epidemics.

iBio

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Using plants as bioreactors to produce proteins for therapeutics - European Pharmaceutical Review

Repertoire Immune Medicines harnesses our immune systems intrinsic ability to cure disease bydecoding relevant Antigen-TCR codes and deploying them as breakthrough immune medicinesin immuno-oncology, autoimmune disorders and infectious diseases

Flagship Pioneering, a life sciences innovation enterprise, announced the launch of Repertoire Immune Medicines, a clinical-stage biotechnology company tapping the curative powers of our immune system to prevent, treat and cure cancer, autoimmune disorders and infectious diseases.

Repertoire Immune Medicines was formed by combining two Flagship companies the innovative and proprietary immune decoding platforms of Cogen Immune Medicines and the immuno-oncology platforms of Torque Therapeutics to create a fully integrated Immune Medicines company. At the helm is Chief Executive Officer John Cox, who most recently led the spin-off of Bioverativ (BIIV) from Biogen (BIIB), and its growth and successful acquisition by Sanofi (SNY).

During the last 4 years, these two Flagship Pioneering originated companies each advanced novel and complementary platforms protected by over 30 patent families. Through their combination, Repertoire Immune Medicines now has the unique capability to decipher human subject-derived antigen-T cell receptor (TCR) codes from healthy or diseased tissues in the context of the major MHC (HLA) types. These complexes dictate T cell activation or exhaustion, and their immunological codes can be used to design and clinically test a multitude of unprecedented therapeutic products based on precedented and specific mechanisms of T cell killing of antigen presenting tumor cells or infected cells.

"Repertoire is pioneering a new class of therapies based on high throughput, high content interrogation of the intrinsic ability of T cells to prevent, or cure diseases," said Noubar Afeyan, Ph.D., Chief Executive Officer of Flagship Pioneering and Co-Founder and Chairman of the Board of Repertoire Immune Medicine. He continued, "our products will be designed to leverage the highly evolved, potent and clinically-validated mechanism of the natural immune synapse to provide immune security to patients. With these ambitious goals in mind, we are pleased to have a proven leader, John Cox, as CEO to realize our shared vision to dramatically improve outcomes for those in need or at risk."

Repertoire has developed a suite of DECODE technologies that allows in-depth characterization of the immune synapse with unprecedented precision. The company leverages its functional response technologies to thoroughly understand the presentation of antigens in disease, de-orphan T cell receptors in the context of single-cell phenotypes, and curate vast amounts of data to enable deep-learning computational prediction models. By coupling single cell technologies with cellular and acellular antigen libraries, the company decodes CD4+ and CD8+ TCR-antigen specificity across selected T cell subsets from patients and from healthy individuals.

"I am pleased to work with the Flagship Pioneering team to integrate these two pioneering companies into a fully formed immune medicines business," said John Cox, Chief Executive Officer of Repertoire Immune Medicines. "Advancing rationally designed immune medicines into the clinic and eventually to commercialization offers tremendous potential for patients and long-term value for our shareholders."

Three DECODE discovery technologies are at the core of the companys immune synapse deciphering platform:

Decoding immune synapses relevant to a particular disease allows Repertoire to deploy the molecular codes to rationally design new immune medicines as disease-fighting TCRs and disease-associated antigens in its therapeutic products.

Repertoires DEPLOY technologies form a product-based platform that includes:

Repertoire is currently engaged in its first dose escalation safety trial with an autologous T cell product TRQ15-01, which leverages its proprietary PRIME platform to prepare the patients T cells and its proprietary TETHER platform to link an IL-15 nanogel immune modulator to the T cells.

The journey for Repertoire Immune Medicines commenced when Flagship Labs scientists contemplated how to rationally and efficiently direct the power of our T cells for therapeutics and cures. One origination group, led by David Berry, M.D., Ph.D., General Partner of Flagship Pioneering, focused on systematically unlocking antigen specific immune control. In parallel, another Flagship origination group, led by Doug Cole, M.D., General Partner of Flagship Pioneering, and based on the cytokine binding work from Prof. Darrell Irvines lab at MIT, focused on using autologous T cells to direct potent immune modulators to the tumor microenvironment.

Story continues

To date, the combined companies raised over $220M to create and develop the DECODE discovery platform and DEPLOY product platform, and to initiate its first clinical trial of PRIME & TETHER T cells in cancer. Repertoires rapid advancement reflects its creative, dedicated and diverse team of over 120 professionals possessing expertise in immunology, experimental medicine, physics, computational science, material sciences, process engineering, bioengineering, protein design and applied mathematics.

ABOUT REPERTOIRE IMMUNE MEDICINESRepertoire Immune Medicines, a Flagship Pioneering company, is a clinical stage biotechnology company working to unleash the remarkable power of the human immune system to prevent, treat or cure cancer, autoimmune conditions and infectious diseases. The company is founded on the premise that the repertoire of TCR-antigen codes that drive health and disease represents one of the greatest opportunities for innovation in medical science. The company harnesses and deploys the intrinsic ability of T cells to prevent and cure disease. Repertoire scientists created and developed a suite of technologies for its DECODE discovery and DEPLOY product platforms that allow in-depth characterization of the immune synapse and the ability to rationally design, and clinically develop, multi-clonal immune medicines. The company is currently conducting experimental medicine clinical trials using autologous T cells primed against cancer antigens and tethered to IL-15. To learn more about Repertoire Immune Medicine, please visit our website: http://www.repertoire.com.

ABOUT FLAGSHIP PIONEERINGFlagship Pioneering conceives, creates, resources, and develops first-in-category life sciences companies to transform human health and sustainability. Since its launch in 2000, the firm has applied a unique hypothesis-driven innovation process to originate and foster more than 100 scientific ventures, resulting in over $30 billion in aggregate value. To date, Flagship is backed by more than $3.3 billion of aggregate capital commitments, of which over $1.7 billion has been deployed toward the founding and growth of its pioneering companies alongside more than $10 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 37 transformative companies, including: Axcella Health (NADAQ: AXLA), Denali Therapeutics (NASDAQ: DNLI), Evelo Biosciences (NASDAQ: EVLO), Foghorn Therapeutics, Indigo Agriculture, Kaleido Biosciences (NASDAQ: KLDO), Moderna (NASDAQ: MRNA), Rubius Therapeutics (NASDAQ: RUBY), Seres Therapeutics (NASDAQ: MCRB), and Syros Pharmaceuticals (NASDAQ: SYRS). To learn more about Flagship Pioneering, please visit our website: http://www.FlagshipPioneering.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200312005102/en/

Contacts

Niki FranklinRacepoint Global on behalf of Repertoire Immune Medicines+1 (617) 624-3264nfranklin@racepointglobal.com

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Flagship Pioneering Announces the Launch of Repertoire Immune Medicines with Industry Veteran John G. Cox as Chief Executive Officer - Yahoo Finance

Such is the extent of our dominion on Earth, that the answer to questions around whether we are still part of nature, and whether we even need some of it, rely on an understanding of what we want as Homo sapiens. And to know what we want, we need to grasp what we are.

It is a huge question, but they are the best. And as a biologist, here is my humble suggestion to address it, and a personal conclusion. You may have a different one, but what matters is that we reflect on it.

Perhaps the best place to start is to consider what makes us human in the first place, which is not as obvious as it may seem.

Many years ago, a novel written by Vercors called Les Animaux Dnaturs (Denatured Animals) told the story of a group of primitive hominids, the Tropis, found in an unexplored jungle in New Guinea, who seem to constitute a missing link.

However, the prospect that this fictional group may be used as slave labor by an entrepreneurial businessman named Vancruysen forces society to decide whether the Tropis are simply sophisticated animals or whether they should be given human rights. And herein lies the difficulty.

Human status had hitherto seemed so obvious that the book describes how it is soon discovered that there is no definition of what a human actually is. Certainly, the string of experts consultedanthropologists, primatologists, psychologists, lawyers and clergymencould not agree. Perhaps prophetically, it is a layperson who suggested a possible way forward.

She asked whether some of the hominids habits could be described as the early signs of a spiritual or religious mind. In short, were there signs that, like us, the Tropis were no longer at one with nature, but had separated from it, and were now looking at it from the outsidewith some fear.

It is a telling perspective. Our status as altered or denatured animalscreatures who have arguably separated from the natural worldis perhaps both the source of our humanity and the cause of many of our troubles. In the words of the books author: All mans troubles arise from the fact that we do not know what we are and do not agree on what we want to be.

We will probably never know the timing of our gradual separation from naturealthough cave paintings perhaps contain some clues. But a key recent event in our relationship with the world around us is as well documented as it was abrupt. It happened on a sunny Monday morning, at 8:15am precisely.

The atomic bomb that rocked Hiroshima on August 6 1945, was a wake-up call so loud that it still resonates in our consciousness many decades later.

The day the sun rose twice was not only a forceful demonstration of the new era that we had entered, it was a reminder of how paradoxically primitive we remained: differential calculus, advanced electronics, and almost godlike insights into the laws of the universe helped build, well a very big stick. Modern Homo sapiens seemingly had developed the powers of gods, while keeping the psyche of a stereotypical Stone Age killer.

We were no longer fearful of nature, but of what we would do to it, and ourselves. In short, we still did not know where we came from, but began panicking about where we were going.

We now know a lot more about our origins but we remain unsure about what we want to be in the futureor, increasingly, as the climate crisis accelerates, whether we even have one.

Arguably, the greater choices granted by our technological advances make it even more difficult to decide which of the many paths to take. This is the cost of freedom.

I am not arguing against our dominion over nature nor, even as a biologist, do I feel a need to preserve the status quo. Big changes are part of our evolution. After all, oxygen was first a poison which threatened the very existence of early life, yet it is now the fuel vital to our existence.

Similarly, we may have to accept that what we do, even our unprecedented dominion, is a natural consequence of what we have evolved into, and by a process nothing less natural than natural selection itself. If artificial birth control is unnatural, so is reduced infant mortality.

I am also not convinced by the argument against genetic engineering on the basis that it is unnatural. By artificially selecting specific strains of wheat or dogs, we had been tinkering more or less blindly with genomes for centuries before the genetic revolution. Even our choice of romantic partner is a form of genetic engineering. Sex is natures way of producing new genetic combinations quickly.

Even nature, it seems, can be impatient with itself.

Advances in genomics, however, have opened the door to another key turning point. Perhaps we can avoid blowing up the world, and instead change itand ourselvesslowly, perhaps beyond recognition.

The development of genetically modified crops in the 1980s quickly moved from early aspirations to improve the taste of food to a more efficient way of destroying undesirable weeds or pests.

In what some saw as the genetic equivalent of the atomic bomb, our early forays into a new technology became once again largely about killing, coupled with worries about contamination. Not that everything was rosy before that. Artificial selection, intensive farming, and our exploding population growth were long destroying species quicker than we could record them.

The increasing silent springs of the 1950s and 60s caused by the destruction of farmland birdsand, consequently, their songwas only the tip of a deeper and more sinister iceberg. There is, in principle, nothing unnatural about extinction, which has been a recurring pattern (of sometimes massive proportions) in the evolution of our planet long before we came on the scene. But is it really what we want?

The arguments for maintaining biodiversity are usually based on survival, economics, or ethics. In addition to preserving obvious key environments essential to our ecosystem and global survival, the economic argument highlights the possibility that a hitherto insignificant lichen, bacteria, or reptile might hold the key to the cure of a future disease. We simply cannot afford to destroy what we do not know.

But attaching an economic value to life makes it subject to the fluctuation of markets. It is reasonable to expect that, in time, most biological solutions will be able to be synthesized, and as the market worth of many lifeforms falls, we need to scrutinize the significance of the ethical argument. Do we need nature because of its inherent value?

Perhaps the answer may come from peering over the horizon. It is somewhat of an irony that as the third millennium coincided with decrypting the human genome, perhaps the start of the fourth may be about whether it has become redundant.

Just as genetic modification may one day lead to the end of Homo sapiens naturalis (that is, humans untouched by genetic engineering), we may one day wave goodbye to the last specimen of Homo sapiens genetica. That is the last fully genetically based human living in a world increasingly less burdened by our biological formminds in a machine.

If the essence of a human, including our memories, desires, and values, is somehow reflected in the pattern of the delicate neuronal connections of our brain (and why should it not?) our minds may also one day be changeable like never before.

And this brings us to the essential question that surely we must ask ourselves now: if, or rather when, we have the power to change anything, what would we not change?

After all, we may be able to transform ourselves into more rational, more efficient, and stronger individuals. We may venture out further, have greater dominion over greater areas of space, and inject enough insight to bridge the gap between the issues brought about by our cultural evolution and the abilities of a brain evolved to deal with much simpler problems. We might even decide to move into a bodiless intelligence: in the end, even the pleasures of the body are located in the brain.

And then what?
When the secrets of the universe are no longer hidden, what makes it worth being part of it? Where is the fun?

Gossip and sex, of course! some might say. And in effect, I would agree (although I might put it differently), as it conveys to me the fundamental need that we have to reach out and connect with others. I believe that the attributes that define our worth in this vast and changing universe are simple: empathy and love. Not power or technology, which occupy so many of our thoughts but which are merely (almost boringly) related to the age of a civilization.

Like many a traveller, Homo sapiens may need a goal. But from the strengths that come with attaining it, one realizes that ones worth (whether as an individual or a species) ultimately lies elsewhere. So I believe that the extent of our ability for empathy and love will be the yardstick by which our civilization is judged. It may well be an important benchmark by which we will judge other civilizations that we may encounter, or indeed be judged by them.

There is something of true wonder at the basis of it all. The fact that chemicals can arise from the austere confines of an ancient molecular soup, and through the cold laws of evolution, combine into organisms that care for other lifeforms (that is, other bags of chemicals) is the true miracle.

Some ancients believed that God made us in his image. Perhaps they were right in a sense, as empathy and love are truly godlike features, at least among the benevolent gods.

Cherish those traits and use them now, as they hold the solution to our ethical dilemma. It is those very attributes that should compel us to improve the well-being of our fellow humans without lowering the condition of what surrounds us.

Anything less will pervert (our) nature.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: David Mark from Pixabay

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Have Humans Evolved Beyond Natureand Do We Even Need It? - Singularity Hub

Reports from theFood and Agricultural Organization of the United Nations,World Health Organization, andothers emphasize the critical role of plant-based diets in creating a sustainable food future for all. Plant-based diets are also key for human nutrition, highlighted in diet guidelines the world over includingUS,Canada, andBrazil. Yet livestock remains essential to aroundone billionof the worlds indigent and theglobal demand for meat and dairy is expected toincrease by 70% by 2050.

Meat production and consumption habits must shift, and solutions are sorely needed to feed the appetite for meat in the US and abroad.

Enter plant-based burgers, which exploded onto the food scene in the 2010s. While eaters love them, questions followed: Are they healthier? More sustainable? And are they even real food?

Opinions are heated, but what does the science show?

A Brave New Burger thats Just Plain Better

Forget bland veggies burgers of yore that only appealed to die-hard vegetarians. Todays food technology methods have brought consumers a beefy patty that sizzlesand theyre a game-changer.

Beyond MeatandImpossible Foodslead the plant-based burger market, and are quite similarin nutrient content and ingredients. A key difference is the use of genetic engineering, used in Impossible to create its umami punch from soy leghemoglobin. Not surprisingly,Impossible eaters care not at all about the tech that made it tastynor should they, given the copious evidence of its safety. (Beyond, conversely, boasts theyre non-GMO.) Major food companies also offer their own plant-based burgers using a variety of techniques and ingredients, now available in supermarkets alongside Beyond and Impossible.

Critics questioned wondered whether plant-based burgers would take off; the marketplace already offers myriad vegetarian choices, after all. Yet contemporary consumersare increasingly seeking ecoconscious options that supplant meat, while delivering the pleasure of eating meatat least, some of the time. Ninety percent of plant-based meat and dairy consumers are omnivores, in fact, and Beyond reports that more than 70 percent of its consumers are meat-eaters seeking a more sustainable option. Importantly, Beyond and Impossible burgers are found on restaurant andfast foodmenus, a good thing since49% of eaters globallydine at restaurants at least weekly, and most choose fast food fare.

Public health and environmental benefits of plant-based burgers are plentiful. Research funded by Beyond Meat and conducted by independent scientists at the University of Michigan found that its burger used 99 percent less water, 93 percent less land, and 46 percent less energy and produced 90 percent fewer greenhouse gas emissions compared to a beef burger; similar results were found in a study of the Impossible Burger. While no peer-reviewed studies are yet available, a significant body of evidencelike this report of 40,000 farms in 119 countries and covering 40 food products that represent 90 percent of all that is eatenshows significantly higher environmental impacts of meat production on land, water, and air compared to plants. While grass-fed beef can be more sustainable, its complicatedand hardly the panacea supporters claim it to be.

And dont forget about antibiotic resistance, among the biggest threats to global health driven largely bymisuse of medicinesin livestock production.

Whatever the individual motivation to select a plant-based burger, the secret sauce is clear: When food tech delivers taste and convenience, health and sustainability win.

Burger Bloviating: Push Back on Plant-Based Meat

As with many food tech innovations, some folks in nutrition and activist circles began disparaging plant burgers as yet another ultra-processed food that consumers dont need. However, there is considerable variation in nutritional quality across the four-categoryNOVA classification(unprocessed and minimally processed foods, processed culinary ingredients, processed, ultra-processed). Andnumerous studiesincluding areportfrom several professional nutrition and food tech organizationsshow that (ultra-) processed foods like bread and canned goods are nutritionally beneficial; its thewhole dietthat matters.

Plus, beef burgers dont grow on trees; the industry employs an extensive set of ingredientsconsumers simply choose not to consider. A wide range ofadditives and preservativesand food processing methods were needed to get that cow ground up onto your bun, for instance, alongside atrocious conditions in industrial animal farming systems. And were you aware that meatpacking is among the most dangerous jobs in the world? The reality is that getting a burger to your table made from animals involves far more processing than one made with plants, facts its polystyrene package doesnt provide.

But is plant-based meat real food? The concept was popularized by journalist Michael Pollan, whose other pithy yet patronizing advice includes eat plants, not food made in plants. Food writer Mark Bittman recently opined, [w]e have to determine whether theyre actually food,likening plant-based burgers to Cheetos. (Seriously?) Other foodies jumped on the bandwagon, creatingnutrition confusionby preaching that meat from animals is inherently superior simply because its from an animal.

At the same time, some health professionals return to the dog-tired diet advice that consumers need to eat more vegetables and fruits, like fresh peas instead of burgers made from pea protein. Similarly, anivory-tower academiccalled plant-based burgers transitional en route to a whole foods diet, ignoring evidence that burgers can be part of a healthy diet, in moderationand are integral to American traditions.

Viewpoints like these reflect a lack of compassion for the realities most people face in just trying to get a meal on the table. They also undermine how difficult it is to change the way we eat, They also discount the vibrant role cuisine plays in culture and disregard the power of technology to meet food needs healthfully and sustainably.

For a Brighter Food Future, Vote With Your Fork

Addressing todays complex food challenges requires all the tools we have to curb climate change, address unsustainable and unjust practices in agriculture, and reduce diet-related chronic diseases. Though novel food technologies will always have haters, its a brave new world with a new generation of eaters.Millennials and Gen Zare highly motivated by health and sustainabilityand both are far more accepting offood technologythan previous generations. Scientific innovations like plant-based burgers will always play a role in shaping human diets,as they always haveand often for the better.

But lets not forget that a burger is a burger is a burgerand its especially tasty with all the fixins. (And fries. Obviously.) Most of us in high-income nations who strive to manage weight, stave off disease, and live longer are better off eating a vibrant salad loaded in fresh veggies, beans, and whole grains rather than a plant-based burger. At least, most of the time.

But you already know that, right?

So when that craving hits, grab a plant-based burger, and enjoy. Voting with your fork is a delicious way to support technologies that will help move forward the food revolution necessary to create a healthy and sustainable food future for all.

P.K. Newby, ScD, MPH, MS, is a nutrition scientist and author whose newest book is Food and Nutrition: What Everyone Needs to Know. Learn more about her at pknewby.com.

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Burger Wars: Beyond Nutrition Idealism and Junk-Science Rhetoric, the Benefits of Choosing Plant-Based are Clear - The Spoon

How do we define organics? From a legal perspective, the term can only be applied to foods that meet a laundry list of requirements set forth by the US Department of Agriculture or similar agencies around the world. But these rules leave no room for technological advances falling under the umbrella of New Breeding Techniquesthat could help us produce foods more sustainably.

Classic genetic engineering relies on transgenics in which genes from one organism is inserted into another. An example: insect resistant soybeans and corn were engineeredto contain Bacillus thuringiensis, commonly known as Bt, a bacterium that occurs naturally in the soil.For years, bacteriologists have known that some strains of Bt produce proteins kill certain insects with alkaline digestive tracts when they try to digest the bacterium. Organic farmers have used Bt in spray form since early in the 20th century. Although anti-GMO activists embrace the use of Bt spray, they have vigorously opposed Bt engineered crops on the grounds that they were created using foreign geneseven though there is no scientific evidence that GMO Bt crops are harmful in any way, and in fact are more sustainable than organic crops that use the spray form.

In almost all cases, NBTs do not involve transgenics. An illustrative example is thegene-edited mushrooma common white mushroom (Agaricus bisporus) engineered using CRISPR to reduce activity of a group of genes that encode an enzyme called polyphenol oxidase (PPO). By deleting just a few base pairs (letters in the language of DNA), the activity of six PPO genes was suppressed, leading to much lower levels of agents called polyphenols. As a result, the modified mushrooms do not brown when left in the air after being cut.

Thats presented a challenge to government oversight officials as to how they should regulate these techniques. Early in 2016, for example, the USDA decided not to regulate a new mushroom made by Penn State University scientists using CRISPR, the popular gene-editing technique.

In aletter to the CRISPR mushroom developerYinong Yang of PSU, the USDA agreed to the non-transgenic status of the mushrooms:

[The Animal and Plant Health Inspection Service (AHIS)] has concluded that your CRISPR/Cas9 edited white button mushroomsdo not contain any introduced genetic material..and APHIS has no reason to reason to believe that the anti-browning phenotype of [the] white button mushroom would increase the weediness of white button mushroom.

Other NBT products now being sold or making their way to the market:

Such crops, however, cannot be sold as organic. That status is defined by organic authorities and in most cases is not related to how things are grown, nor to whether the crop is produced sustainably. Indeed, in some cases, crops developed through NBTs can be grown with less potentially harmful inputs than those granted organic status.

This disconnect between sustainability and organic certification is likely to persist in the foreseeable future because the standards that are used to designate which farm products receive an organic seal are based on, or at least influenced strongly, by ideological forces. The main such force in this case, promoted by organic authorities, is a belief that classic organic techniques are more environmentally sensitive than newer techniques, which they claim are untested and potentially dangerous.

This belief is not substantiated and scientists who work on food biotechnology have published studies in recent years making the point that cutting edge biotechnology is in many cases more organic (for lack of a better term) than techniques utilized on organic farms. Consequently, they maintain, farmers should be allowed to embrace NBTs, not only for the sake of earning better profits and producing higher quality food, but to improve sustainability mostly by reducing carbon footprints and the toll on the land. It is ironic that farmers who might embrace NBTs would be more true to agro-ecological principals and practices than those whove been granted the use of organic labels for following techniques that are, in some cases, more than a century old and based on outdated ideas of what is sustainable.

Its really quite simple. Practices are more sustainable if they cause less harm to the environment in order to produce a given amount and quality of food compared with alternative practices. Thus, if an NBT version of a particular plant crop is resistant to a certain plant pathogen that ruins that crop, or if the NBT can be grown with less water or less fertilizer, or if it uses less land than the comparable non-NBT, then the NBT is more sustainable. Similarly, if an NBT reduces a crops carbon footprint, this too translates into improved sustainability. Since the current framework excludes from organic certification crops whose genes, or their expression, have been tweaked via any kind of genetic engineering, including NBTs, we are left with the hard reality that organic certification does not equate with sustainability.

The idea that NBTs could improve the sustainability profile of organic farming is the subject of a paper by two agricultural plant scientists in Italy Luca Lombardo and Samanta Zelasco of the Institute for Sustainable Plant Protection, Italian National Research Council and the Olive Growing and Olive Oil Industry Research Centre, Agricultural Research Council.

The authors supply a definition of sustainability at the beginning of the paper, published in the journal Sustainability: Organic farming (OF) systems are conceived to produce food through the integration of cultural, biological, and mechanical practices aimed at preserving natural resources, biodiversity animal welfare, and eventually human health.

After outlining the basis of transgenic techniques, the authors move into areas that fall within the NBT realm, the first one being Genome Editing with Engineered Nucleases (GEEN).GEENS include older technologiesdeveloped in the early 2000s or slightly earlier, such as hybrid meganucleases, zinc finger nucleases (ZFNs), and transcription activator like effectors nucleases (TALENs). They include what has become the most widely-used genome editing technology, CRISPR.

In recent years, CRISPR and other new technologies have jump-started a revolution in numerous life sciences, with biomedical research a particular spotlight. Along the way, the technology has raised concerns about whether there should be limits on its use,particularly when it comes to germline editing of humans, and making changes that in some cases could possible be passed along to future generations.

In 2017, researchers at Oregon Health Sciences University, in Portland, demonstrated that they could use CRISPR on human embryos to correct a genetic abnormality underlying hypertrophic cardiomyopathy, a serious inherited heart condition. Soon after, researchers in China described success with a similar approach on human embryos to correct beta thalassemia, a genetic blood disease.

But while much of the public attention and controversy have focused on the use of CRISPR to modify humans to prevent diseases, CRISPR is at center stage in a revolution in the application of genetic engineering to agriculture, including plant and fungal crops and farm animals.The benefits of CRISPR over the other NBT technologies is that it is programmableit can be used to modify, delete, or insert any genetic sequence with by swopping cheaply made strands of whats called RNA, while ZFNs and TALENs must be custom-made for any genome editing job. But each technology has particular pluses and minuses, depending on the job need.

Conventional plant breeding techniques can generate desirable traits, but the outcomes are difficult to predict. Depending on the species, development of a plant with novel characteristics can take 7 to 13 years to produce stable, uniform plant varieties. NBTs, CRISPR in particular, allow production of new varieties of plants fungi and animals but with increased precision and much shorter time periods t
han in conventional breeding. Other benefits include improved nutritional properties, new tastes, reduced levels of allergens, disease resistance and increased shelf-life.

A study in the journal Plant Breedingsuggests that the new techniques may lend themselves well to exclusion from regulation by agencies that have tightly controlled transgenic technologies. This could encourage food manufacturers. However the bottom line is typically consumers. In this regard, there is a major hole in the argument, advanced by some, that if farmers embrace advanced engineering techniques and produce more sustainable crops, health-conscious consumers will embrace these new crops. Farmers taking this route without buy-in from consumers and food companies do so at the expense of the organic seal, at least in the current regulatory milieu. Regardless of whether that organic seal really means anything from a sustainability perspective, or for that matter from a nutritional perspective, it means something from a branding and financial perspective. At least in part, farmers desire the organic seal, because consumers are willing to pay premium prices.

Lombardo and Zelasco also considered polling data published in Europe and in the US which make a case that cisgenic crops (made using NBTs) are more likely than transgenic crops to gain acceptance by consumers who traditionally have sought out organic food. Furthermore, unlike transgenic crops that non-governmental organizations can detect with easy-to-use testing kits, cisgenic crops are not distinguishable. This does not mean, however, that regulatory agencies in Europe or in the US will regulate cisgenic crops based on their content with no regard for the methods used to create them.

A version of this story originally ran on the GLP on May 29, 2018.

David Warmflash is an astrobiologist, physician and science writer. Follow him on Twitter @CosmicEvolution

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The real sustainability revolution in farming rests with CRISPR and other New Breeding Techniques. Why are organic farmers blocked from using them? -...

The legendary Bulletin of the Atomic Scientists (BAS), which tracks issues related to technology and global security, has issued a terrifying warning: We are less than two minutes to midnight on the Doomsday clock. Its very bad news, representing the most dangerous situation that humanity has ever faced.

What makes this moment so perilous? The scientists statement includes warnings over the cyber-weaponization of information, the spread of artificial intelligence (AI) in making military decisions, the destruction of treaties meant to limit the spread of nuclear weapons, the abandonment of global agreements to limit climate chaos, the spread of genetic engineering and synthetic biology technologies, and more. It does not account for the escalated likelihood of atomic reactor disasters, but based on at least one BAS publication, it should.

Since 1947, this prestigious band of elite scientists and global thinkers has been putting out a clock meant to time the peril of a global apocalypse. First issued at the dawn of the Cold War, it has mostly focused on the dangers of atomic warfare. Its countdown to Armageddon has been set as far away as 17 minutes from midnight, a hypothetical time of human extinction. That relatively optimistic assessment came in 1991, with the fall of the Soviet Union and the definitive end of the Cold War.

Get the latest news and thought-provoking analysis from Truthout.

In 2018, the BAS set it at two minutes, the closest to catastrophe it had ever been. They repeated that estimate in 2019. But this years announcement has taken us inside the two-minute warning with a hair-raising litany of likely lethal catastrophes set to occur within 100 theoretical seconds.

Donald Trump is mentioned only once by name, in conjunction with his decision to trash the Paris Accords on climate change and greenhouse gas emissions. The scientists urge whoever wins the 2020 election to reinstate the U.S. commitment limiting carbon and other climate-destroying emissions. The BAS also cites Brazilian dictator Jair Bolsonaro for his decision to allow the destruction of the Amazon, with huge impacts on climate.

The BAS strives to maintain a non-partisan image. But Trumps presence in the White House clearly hangs over any assessment of humankinds survivability. The specter of his finger on the nuclear, ecological and financial buttons for the next four years hangs over humankind like a pall but goes otherwise unmentioned in this Doomsday assessment.

Also unmentioned is the question of more than 450 atomic power reactors worldwide. A small but vocal outlier coterie has argued that nuclear energy combats global warming by emitting less carbon that coal burners. But the Bulletin recently enshrined a major assessment by the esteemed Dr. Robert Jay Lifton, warning that commercial reactors pose a serious threat to human survival on this planet.

Published in August 2019, The false promise of nuclear power in an age of climate change argues that the 450 atomic reactors now deteriorating worldwide pose an existential threat to our survival. Writing with Professor Naomi Oreskes, Lifton warns that atomic energy is expensive and poses grave dangers to our physical and psychological well-being. Citing costs of nuclear juice at $100 per megawatt-hour versus $50 for solar and $30-40 for onshore wind, the authors say that the industry suffers from a negative learning curve, driving nuke costs constantly higher while those for renewables head consistently down.

Citing the unsolved problem of radioactive waste management, the BAS article warns of the ongoing impacts of major disasters like Fukushima and Chernobyl (and potentially more to come), whose fallout kills humans and does untold damage to the global ecology. Lipton and Oreskes say we need to free ourselves from the false hope that a technology designed for ultimate destruction can lead to our salvation. They favor making renewable energies integral to the American way of life.

In addition to nuclear and climate issues, the 2020 Doomsday assessment emphasizes some relatively new concerns. In the last year, it says, many governments used cyber-enabled disinformation campaigns to sow distrust in institutions and among nations, undermining domestic and international efforts to foster peace and protect the planet.

By attacking both science and the fabric of international peace accords, some global leaders have created a situation that will, if unaddressed, lead to catastrophe, sooner rather than later.

That situation includes AI and hypersonic warfare, both escalating at a frenzied pace. Now used in ultra-fast attacks, AI is dangerously vulnerable to hacking and manipulation while making kill decisions without human supervision. In nuclear command and control systems, the BAS warns, research and experience have demonstrated the vulnerability of these systems to hacking and manipulation.

This is an absolutely terrifying brew. The spread of disinformation, the contempt for science and expert opinion, the undermining of global agreements on arms control, and climate change are all deadly. Add in the new world of AI and hyper-sonic warfare, then pile on autocrats like Trump and Bolsonaro, and finish with the certainty of more disasters from 450 crumbling, obsolete atomic reactors.

All in all, its small wonder the Bulletin has taken us past the two-minute warning. It will clearly take every ounce of our activist strength to save our species from the final whistle.

Continued here:
Trump's Presidency Brings Us Closer to Midnight on the Doomsday Clock - Truthout

Bellarmine Nneji

Education remains the bootstrap of both human and national developments. It is the solvent to the myriads of societal and economic challenges. As the world marks the International Day of Education, there is need to ensure that education both at national and international levels match and address the current local and global challenges.

According to the UNESCO, the theme for this year is Learning for people, planet, posterity and peace. This years theme calls for a multidisciplinary approach to teaching and learning, a multidimensional approach to societal problems and challenges, a concerted effort and sincerity of purpose from both governments and individuals. It is also a direct clarion call for education for sustainability. Sustainability is a word that is loaded with meanings and responsibilities. Bearing this in mind, this years theme appears holistic in that it stresses the fact that the survival and extension of humanity is dependent on people acquiring the right education for the sake of survival and extension of the human race. Thus education that is adequate for the current national and global challenges must focus on the preservation and sustenance of the planet earth both for the present humans and posterity. This challenge to preserve and sustain the present humans and posterity can only be possible if there is peace at all levels and societies of the globe. The reality of this is that violence and similar acts which deny the society of peace has butterfly effects across the globe. It has both spiral and trickle down effect.

The summary of this years theme is a call for values orientation and reorientation. Education remains a major route to this. This challenge needs a revisit to our traditional pedagogic and andragogic approaches and routines. A critical analysis of the theme is a good starting point.

Education and learning for people is to ensure that the curriculum has objectives of ensuring that we learn to appreciate our humanity. Humanity has been dangerously challenged that we no longer know what it means to be human. We are becoming more like, if not worse than, animals. Ironically some who think and believe that they are not animals see others as animals and treat them so. Individuals are kidnapping their fellow citizens sometimes killing them if no ransoms are paid. Even younger ones are involved in the get-rich-quick syndrome which has graduated from the former yahoo yahoo swindling to the current yahoo yahoo rituals. Humanity is commodified. Some are now involved in organ selling. Also some Governments across the globe no longer have regard for people. Incarcerations are becoming the order of the day. Citizens are being treated like puppets. We also live like people who have no future. We think only of the moment. There is need to appreciate diversity. Every Nigerian needs to have an ideas of what it means to respect life and the associated human rights. Civic education at all levels must reflect this. There must be sanctity of life.

As we learn to have regard for people and humanity we need to appreciate the fact that we live on a fragile spot known as the planet earth which is diminishable and with limited and diminishable resources. There is need for this understanding. The educational curricula should ensure that there is need for appreciation of prudent use and management of available resources. The introduction of environmental-appreciation-related courses like environmental ethics should be incorporated at all levels of education for this special purpose. Environmental sustainability is a challenge for all. However there is need to understand and appreciate the justification for prudent management of planetary resources in the face of opposition by climate contrarians and those who believe that planetary resources are infinite. There is need to balance our material quests for prosperity and the challenge for sustenance. Many are yet to appreciate the enormity of the challenges posed by climate change. The impacts are already with us. There is to appreciate the reality the challenges faced by the planet earth.

The need for education and learning to appreciate our humanity and also to protect and sustain our planet earth are all geared towards the present generation but most importantly for the sake of posterity. What we the present humans should understand is that we were once people categorized as posterity. If we had inherited an inhabitable and nonconducive planet, we wouldnt be as we are today. Our genes could have been distorted. This is just one of the strands of logic for education and learning for posterity through sustainability (education for sustainability). We owe posterity a healthy planet. Education for posterity (as an aspect of this years theme) is not only from the perspective of sustainability of the planet earth but also from the perspective of extension of humanity. Humanity is challenged already by extinction and certain posthuman drifts through technology and its advancements. The present human race is being challenged by what may be rightly called technological beings. The current species of human beings may become the minority to be discriminated against in the nearest future. Genetic engineering is seen as both a disease and a cure. This is what deconstruction philosophers call pharmakon. This calls for the introduction of technology ethics or philosophy of technology into the curriculum of all technology institutions and departments across the globe. This will help to ensure that technological developments and innovations have human faces. Our policy makers should be wary and circumspect of technologies and its advancements. There is need to adopt the precautionary principles in the areas of genetic engineering with special references to genetically modified organisms and products. The cases of Monsanto and Dupont remain eye openers. Side effects of certain contentious issues sometimes take more time than the period of study and trials to emerge. Thats the message of the precautionary principle.

It is only people that are humans that can understand how to treat people like human beings and persons. It is also human beings that will understand the need to preserve the planet and ensure intergenerational equity. We owe a lot to posterity.

In all, the entire quests become a mirage and the challenges become herculean if there is no peace. Peace remains one of the necessary and sufficient conditions for the realization of the entire quest of the theme for this years World International Day of Education.

Education for peace demands a lot. There is need for appreciation of cultural and religious diversities. Terrorism has become a global threat that is unsettling many societies. There is need for nipping this from the bud. Education for peace and antiterrorism needs orientation in critical thinking. Uncritically individuals are easily recruited into terrorism and its organizations. The curriculum should emphasize the need for Learning to Live Together. This has been one of the four pillars of education according to UNESCO. There is need for tolerance. We are one humanity irrespective of creed. Inclusive humanism and critical thinking should prevail in our educational curricula.

Nneji writes from Lagos

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The International Day of Education - Daily Sun

That next day, Drake preferred sleeping over eating. But then, thats common with newborns. Tarah and Eric would wake him for feeding, careful to make sure he got plenty of nourishment.

By Saturday, these experienced parents became uneasy. Drake was just too lethargic. It was harder to wake him for feedings. The OSullivans called Drakes doctor and were assured there was nothing to be concerned about; Drake had been healthy when he left the hospital two days ago. And, the doctors office assured them, they would be checking him again on Monday at a scheduled office visit.

But the OSullivans disquiet grew by the hour. By Sunday evening, Drake would not open his eyes or respond to them. He was growing limp and struggling to breathe. The OSullivans rushed Drake to the hospital where the staff flew into emergency mode. Too sick for care at the local hospital, Drake was stabilized for transport to the pediatric intensive care unit (PICU) at Greenville Memorial Hospital. Just 72 hours after birth, Drake lapsed into a coma. And no one knew why.

That unforgettable night was the beginning of a long journey of test after test and a diagnosis by elimination.

Drake continued to decline as each negative test pushed aside another horrible possibility. You would think that eliminating terrible diseases would be a good thing, says Eric. But that just meant we were looking at something very rare.

Finally, blood tests revealed an ever-elevating level of glycine in Drakes blood, a symptom of an extremely rare, genetic metabolic disease called nonketotic hyperglycinemia or NKH.

The words nonketotic hyperglycinemia meant nothing to Tarah and Eric. But the next words were clear: Drake had a less than 10 percent chance of survival.

The diagnosis was like a starters pistol for the OSullivans. From that moment, everything would be a race against time to save Drake.

After 28 days of tests, monitors, tubes and wires, Drake was released to go home. There, as Tarah explains, Our house became a sort of lab. There were blood tests, feedings, medications and monitoring day and night, 24/7. Glycine became the OSullivans obsession as they tried desperately through medication and diet to moderate Drakes levels. They began to search for information, research, treatment, medical advice anything to save his life.

The OSullivans contacted anyone who might know about NKH, have a related research project or could tell them more. They learned that NKH affects fewer than 500 people worldwide and has no cure. There was no research underway, and no funding for research. And because there is no medically recognized cure for NKH, all treatments are considered experimental and not covered by medical insurance. Period.

So Tarah became a lay scientist. She read everything, called and emailed medical researchers and established the Drake Rayden Foundation to raise awareness for NKH, fight for better treatment and support research. She entered a world of genetics and vectors, glycine and metabolic pathways. Tarah had quit college just shy of completing her business degree. Now she desperately needed the scientific expertise that would help her understand the disease and find the cure.

Tarah decided to return to college.

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The Face of Science - Clemson World magazine

Cuba is advancing in the development of a therapeutic HIV/AIDS vaccine that has concluded the preclinical studies phase in lab animals and testing in about 20 human volunteers, with results of safety, tolerance and without adverse effects, according to the project leaders.

The product named Teravac-HIV is essentially aimed at inducing an anti-HIV cellular response to reduce the burden of the virus on patients by promoting a functional cure, said principal project specialist Enrique Iglesias.

Cuba has a low incidence of HIV/AIDS epidemic, but there is a high resistance to some of the antiviral compounds we use. In that context, a therapeutic vaccine could contribute to the management of the epidemic, Iglesias told the state newspaper Juventud Rebelde in an article published this Sunday.

There are 26,952 persons on the island infected with the HIV/AIDS virus, 80 percent are male and 82 are between 20 and 54 years old, according to the latest official data on the epidemic released last week.

Of these, 86 percent receive free and controlled antiretroviral therapy, based on a combination of Cuban and other imported antiretroviral drugs, certified by the World Health Organization.

Among those diagnosed, the most affected are transsexual women, with 19.7%, men who have sex with other men (MSM)5.6%and people who practice prostitution, which are 2.8%.

Cuba starts giving out free preventive HIV pill

A genetically engineered vaccine

The Cuban Doctor in Biological Sciences said that the vaccine candidate that the Center for Genetic Engineering and Biotechnology (CIGB) has been developing for several years contains three genetically engineered proteins.

One of these proteins generates the specific immune response against the virus, and two other hepatitis B virus (HBV) proteins were includedone is the active ingredient of the prophylactic vaccineand both can generate immunity against HBV.

The specialist said that at the end of the research phaseof preclinical and toxicological tests in lab animalsa study was designed that included more than 20 HIV-positive patients in good health distributed in two groups.

One group received intranasal and subcutaneous inoculations with Teravac and the other with a placebo. The results of the vaccine candidate showed its safety and tolerance without significant adverse events being reported, said the specialist.

He also indicated that future studies should be aimed at optimizing the dose and immunization plan, among other variables, before there can be certainty of the effectiveness of the vaccine.

Although it is recognized as partially effective, some of the benefits of the future therapeutic vaccine are that it could reduce the financial cost of the therapies, allow their temporary recesses to counteract their side effects and could also reduce transmission by sexual contact.

In addition, it is credited with the possibility of reducing viral diversity in patients, as well as the appearance of resistance mutations, which would enhance the effectiveness of therapies.

Coinciding with the world day against AIDS this December 1, the islands public health authorities affirm that Cuba is the country in Latin America with the lowest prevalence of the virus, and highlighted that they maintain control in transmission in children under 14, heterosexual men and women, among other results.

TERAVAC-VIH: solucin cubana contra el SIDA?

Continued here:
Cuba advances in therapeutic HIV/AIDS vaccine project - OnCubaNews

For all of the wondrous potential of immunotherapies, there have been some notable obstacles in the early goings. Engineering immune cells to attack cancerous tumors can lead to solid results shortly after administering a dose, but for many patients the effects wear off once rapidly mutating tumor cells acquire new defense mechanisms.

Cellectis (NASDAQ:CLLS) thinks it may have a partial solution. In mid-November, the gene editing company published the results from a proof of concept study for its "smart" immunotherapy approach. Is the technique the future of cellular medicine?

Image source: Getty Images.

Today, cellular oncology therapies genetically engineer immune cells to bolster their safety and efficacy as a cancer treatment. There are T cells, natural killer (NK) cells, tumor infiltrating lymphocytes (TILs), and others. They're often engineered with chimeric antigen receptors (CARs) or T cell receptors (TCRs), which allow them to home in on and suppress specific genes in cancer cells.

While current-generation CAR T cells or CAR NK cells are capable of mounting formidable attacks on tumors at first, treatment responses aren't durable for all patients. That's because cancer cells mutate to rely on different proliferation genes, or secrete new molecules into the tumor microenvironment that neutralize immune cells. Meanwhile, overstimulating the immune system can reduce the potency of immune cells and lead to devastating side effects, such as cytokine release syndrome.

That prompted Cellectis to design "smart" CAR T cells capable of adapting to changes in the tumor microenvironment. In a proof of concept study, the company utilized synthetic biology concepts to rewire genetic circuits in three different genes of the initial T cells.

One edit made the immunotherapy more potent, but in a controlled manner to reduce off-target toxicity. The other two edits imbued CAR T cells with the ability to secrete inflammatory proteins inside the tumor microenvironment in proportion to the concentration of cancer cells.

In other words, the smart CAR T cells only asked for help from the rest of the immune system when it was needed most, which increased the anti-tumor activity of treatment and made native immune cells less likely to become neutralized. That should reduce the likelihood of triggering cytokine release syndrome, the most common (and potentially fatal) side effect of cellular medicines, which is caused by high concentrations of immune cells.

The study was conducted in mice, which means the safety and efficacy observations can't be extrapolated into humans. But that wasn't the point. The proof of concept demonstrates that the basic idea of engineering tightly controlled genetic circuits into immunotherapies is feasible. It could even allow multiple genetic circuits of the same drug candidate to be tested against one another in parallel, hastening drug development and lowering costs. Is it the inevitable future of cellular medicine?

Image source: Getty Images.

Gene editing tools are required to engineer immune cells. In fact, immunotherapies are the lowest hanging fruit for gene editing technology platforms today. It's simply easier to engineer immune cells in the lab (ex vivo) than it is to engineer specific cell types in the complex environment of the human body (in vivo).

That explains why nearly every leading gene editing company has immunotherapy programs in its pipeline. Coincidentally, all of the leading drug candidates in the industry pipeline are off-the-shelf CAR T cells engineered to treat CD19 malignancies such as non-Hodgkin's lymphoma (NHL) and B-acute lymphoblastic leukemia (B-ALL), regardless of the gene editing approach used. The smart CAR T cells designed by Cellectis targeted CD22 malignancies, but the approach could be adapted to CD19 antigen.

Developer(s)

Drug Candidate

Gene Editing Approach

Development Status

Cellectis and Servier

UCART19

TALEN

Phase 2

Precision BioSciences (NASDAQ:DTIL)

PCAR0191

ARCUS gene editing

Phase 1/2

CRISPR Therapeutics (NASDAQ:CRSP)

CTX110

CRISPR-Cas9

Phase 1/2

Sangamo Therapeutics (NASDAQ:SGMO) and Gilead Sciences (NASDAQ:GILD)

KITE-037

Zinc finger nuclease

Preclinical

Data source: Company websites.

Will these companies eventually turn to "smart" immunotherapies with regulated genetic circuits? It does seem inevitable, especially if the approach can reduce or eliminate cytokine release syndrome and enable more durable responses.

For example, Cellectis reported that all seven patients taking part in the phase 1 trial of UCART19 suffered from at least grade 1 cytokine release syndrome, which caused complications that led to the death of one patient. Five of the seven patients achieved molecular remission, but one relapsed (and remained alive) and one died. To be fair, all patients taking part in the trial had advanced, heavily pretreated B-ALL.

Precision BioSciences has encountered similar obstacles in an ongoing phase 1/2 trial of PBCAR0191. The company's lead drug candidate was administered to nine patients with NHL or B-ALL. Three cases of cytokine release syndrome were reported, but all were manageable. Seven responded to treatment, including two that achieved a complete response, but three eventually relapsed.

CRISPR Therapeutics recently began dosing patients with CTX110 in a phase 1/2 trial that will eventually enroll up to 95 individuals, but initial results won't be available until 2020. Sangamo Therapeutics and Kite Pharma, a subsidiary of Gilead Sciences, are plowing ahead with zinc fingers,but are still in preclinical development.

Investors seem pleased with most of these gene editing stocksright now. After all, despite the obstacles, current-generation cellular medicines are delivering impressive results in patient populations with relatively few options. But upcoming data readouts could easily differentiate the pack. That could increase the need to invest in augmented capabilities, such as smart immunotherapies.

There's plenty of untapped potential in cellular medicine. Today, companies are developing drug candidates with engineered CARs and TCRs designed to test hypotheses about the function of immunotherapies. As approaches find success, measured in safer and more durable responses, the next layer of complexity will be added in an effort to find even more successful therapies. And the cycle will continue.

Therefore, it seems inevitable that the field of cellular medicine will turn to smart immunotherapies with more complex genetic edits, much like the field quickly embraced the need for engineered immune cells and off-the-shelf manufacturing processes. That said, the immediate focus for Cellectis and its peers is building a stable foundation -- and those efforts have only just begun.

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Did Cellectis Just Provide a Glimpse of the Future of Cellular Medicine? - The Motley Fool

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Global and Regional CRISPR And CRISPR-Associated (Cas) Genes Market 2019 by Manufacturers, Regions, Type and Application, Forecast to 2025 - Daily...

PeakPx

Mark Zuckerberg founded Facebook when he was 19 years old. By 25, his company was valued at over $5 billion. At 28, he took Facebook public. Now, at the age of 35, he is among the top 10 richest people in the world.

When we think of entrepreneurs, we tend to think of the Mark Zuckerbergs of the world youthful visionaries who disrupt traditional businesses with a new and better ways of doing things.

New research, however, challenges the view that youth is advantageous to entrepreneurial success. Perhaps a better entrepreneurial archetype is that of Herbert Boyer. Boyer founded Genentech at the age of 40 based on his breakthrough discoveries in genetic engineering. Or, consider the story of David Duffield. Duffield founded Workday, a financial and human capital management software company, in his 60s, after spending a career in application software. Now, Workday has a market capitalization of over $40 billion.

The data is increasingly showing that its never too late to start a business. Below are five research-backed reasons why entrepreneurial success may come quickest to those who wait.

1) The stereotype of the very young and very successful entrepreneur is exactly that a stereotype.

It turns out that the media may be the biggest culprit in perpetuating the belief that entrepreneurship is a young mans game. For example, the website TechCrunch gives annual awards to the most compelling startups, internet and technology innovations of the year. The average age of award recipients from 2008 to 2016 was 31. Inc. magazine and Entrepreneur magazine also publish lists of entrepreneurs to watch. In 2015, the average age of entrepreneurs who made this list was 29. Compare that to the average age of a typical startup founder (42) to see the discrepancy.

2) Not only are older entrepreneurs more common, they are more successful.

42 is the average founder age of all S-corporations, C-corporations, and Partnerships that registered in the United States between 2007 and 2014. Examining the performance of these companies reveals yet another trend: companies with older founders tend to outperform companies with younger founders. Looking at the top 1% of startups (in terms of company performance), the average founder age increases to 43. Looking at the top 0.1%, the founder age increases even more, to 45. Moreover, the average age of startup founders who achieved a successful exit (as defined by an acquisition or an IPO) is 47.

3) Entrepreneurs working in major entrepreneurial hubs are no younger than other entrepreneurs.

Another misconception is that startup founders practicing in the hottest entrepreneurial hubs think Silicon Valley and New York City are younger than in other areas of the country. Again, the data does not show this to be the case. The average age of entrepreneurs in California, Massachusetts, and Silicon Valley is also 42. And, in New York City, the average entrepreneurial age is only one year younger than average (41).

4) The average age of new entrepreneurs entering the market over the past decade has increased.

Given the rise of technology and technology-related entrepreneurship, one might guess that the average entrepreneurial age has fallen in recent decades. Again, the data suggest the opposite. The average founder age has risen from 41.8 in 2007 to 42.5 in 2014.

5) Certain fields attract entrepreneurs that are older than average.

Not surprisingly, there is truth to the idea that technology is a young mans game. However, the age spread is not as wide as one might think. For instance, startup founders operating in the software publishing industry are, on average, 40 years old (two years younger than the overall average). That said, there are other fields that attract older entrepreneurs. For example, the average age of founders in the pipeline transportation of natural gas, basic chemical manufacturing, and paint, coating, and adhesive manufacturing industries are 51, 48, and 48, respectively. Startup founders operating in oil and gas extraction and engine, turbine, and power transmission equipment manufacturing are also significantly older than other types of entrepreneurs.

Conclusion. The novelist George Eliot famously said, Its never too late to be what you might have been. This is sage advice for all aspects of life, but it might be especially relevant in the case of entrepreneurship.

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Five Reasons Why Its Never Too Late To Start A Business - Forbes

XconomyBoston

A cancer tumor is a veritable patchwork of cells with a variety of genetic fingerprints.

Immunitas Therapeutics is using single-cell genomicsan approach that studies the genetic activity of individual cellsto peer deeply into patient tumors and more precisely determine what is fueling the growth.

With that knowledge, the company plans to develop new targets for treating forms of the disease based on what it learns about the interactions between immune cells and cancer cells around tumors.

Now the Boston company has raised $39 million to advance compounds discovered with its computational platform into human testing by the end of 2022.

The startup was founded by venture capital firm Longwood Fund, itself started about a decade ago by a trio of biotechies who worked together at Sirtris Pharmaceuticals through its 2008 acquisition for $720 million by British drug giant GlaxoSmithKline (NYSE: GSK).

Lea Hachigian, a Longwood principal, is president of Immunitas. She told Xconomy that Longwood found out about the platform, which had been developed and in use in the labs of its scientific cofounders for about three years, this winter.

The progress it had madeImmunitas already has multiple potential monoclonal antibody treatments in its pipelineprompted the venture firm to turn the tech into a company.

Treatments for cancer based on the genetic signature of a tumor, known as checkpoint inhibitors, have been able to help many cancer patients who previously had few options for treatment. But those treatments are only relevant for about 15 percent to 20 percent of cancer patients, Hachigian says.

Combination approaches, in which drug developers mix and match some of those therapies, havent proven to be a panacea either.

Those approaches are exciting, but they have been limited so far in what theyve yielded in the clinic in terms of efficacy, she says.

There a bunch of patients who havent been able to benefit from some of these treatments, she saysand those are the people for whom Immunitas is aiming to develop new treatments.

It plans to analyze cells from specific patient subgroups, such as people with a well-defined form of a disease or those who have developed resistance to a certain kind of treatment. The companys technology has also led it to identify biomarkers that it intends to use to guide its selection of patients for clinical trials. The idea is that a drug developed from those samples would be targeted at that group.

It is also looking to set itself apart from other drug discovery efforts by analyzing human samples, avoiding the misleading signals that can be sent by animal tests.

Single cell genomics pioneer Aviv Regev, a computational biologist and core member of the Broad Institute of MIT and Harvard, was an early collaborator on the project.

Hachigian likened the platform to noise-canceling headphones for tumor biology in how it allows researchers to hone in on drivers of tumor progression.

The companys lead program is designed around a target Immunitas discovered by studying a tumor that is resistant to an existing treatment. Since then it has determined the target is overexpressed in other tumor types, too, both liquid and solid.

Hachigian says the companys deep immunology expertise also set it apart from others using single-cell genomics to find cancer drugs. One of its scientific founders, Kai Wucherpfennig, heads the Dana-Farber Cancer Institutes department of cancer immunology and virology. (Its others are Mario Suv, a physician-scientist in the department of pathology at Massachusetts General Hospital; and MITs Dane Wittrup, the Carbon P. Dubbs Professor in Chemical Engineering and Biological Engineering.)

Immunitas isnt the only startup thats looking cell by cell in hopes of making new biological discoveries that lead to treatments. Regev, in fact, is a co-founder of Cambridge, MA-based Celsius Therapeutics, another new company using single cell genomics to advance its drug discovery efforts.

Celsius launched last year with $65 million in Series A funding led by Third Rock Ventures.

In addition to Longwood, two big pharma companies are among Immunitass biggest backers. Its Series A was led by Leaps by Bayer and Novartis Venture Fund, those companies respective venture arms. Other institutional investors in the round include Evotec, M Ventures, and Alexandria Venture Investments.

The company has five full-time employees and is based in BioLabs, an incubator in Kendall Square. By the end of next year, it plans to have added another 10 or so. And the following year, when it projects it will move into human testing, Immunitas plans to tack on perhaps another 10 more employees to fuel its clinical development efforts.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

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With Cell-By-Cell Take on Drug Discovery, Immunitas Debuts With $39M - Xconomy