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Category Archives: Human Genetic Engineering

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


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

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Youve heard of CRISPR, now meet its newer, savvier cousin CRISPR Prime – TechCrunch

CRISPR, the revolutionary ability to snip out and alter genes with scissor-like precision, has exploded in popularity over the last few years and is generally seen as the standalone wizard of modern gene-editing. However, its not a perfect system, sometimes cutting at the wrong place, not working as intended and leaving scientists scratching their heads. Well, now theres a new, more exacting upgrade to CRISPR called Prime, with the ability to, in theory, snip out more than 90 percent of all genetic diseases.

Just what is this new method and how does it work? We turned to IEEE fellow, biomedical researcher and dean of graduate education at Tuft Universitys school of engineering Karen Panetta for an explanation.

CRISPR is a powerful genome editor. It utilizes an enzyme called Cas9 that uses an RNA molecule as a guide to navigate to its target DNA. It then edits or modifies the DNA, which can deactivate genes or insert a desired sequence to achieve a behavior. Currently, we are most familiar with the application of genetically modified crops that are resistant to disease.

However, its most promising application is to genetically modify cells to overcome genetic defects or its potential to conquer diseases like cancer.

Some applications of genome editing technology include:

Of course, as with every technology, CRISPR isnt perfect. It works by cutting the double-stranded DNA at precise locations in the genome. When the cells natural repair process takes over, it can cause damage or, in the case where the modified DNA is inserted at the cut site, it can create unwanted off-target mutations.

Some genetic disorders are known to mutate specific DNA bases, so having the ability to edit these bases would be enormously beneficial in terms of overcoming many genetic disorders. However, CRISPR is not well suited for intentionally introducing specific DNA bases, the As, Cs, Ts, and Gs that make up the double helix.

Prime editing was intended to overcome this disadvantage, as well as other limitations of CRISPR.

Prime editing can do multi-letter base-editing, which could tackle fatal genetic disorders such as Tay-Sachs, which is caused by a mutation of four DNA letters.

Its also more precise. I view this as analogous to the precision lasers brought to surgery versus using a hand-held scalpel. It minimized damage, so the healing process was more efficient.

Prime editing can insert, modify or delete individual DNA letters; it can also insert a sequence of multiple letters into a genome with minimal damage to DNA strands.

Imagine being able to prevent cancer and/or hereditary diseases, like breast cancer, from ever occurring by editing out the genes that are makers for cancer. Cancer treatments are usually long, debilitating processes that physically and emotionally drain patients. It also devastates patients loved ones who must endure watching helpless on the sidelines as the patient battles to survive.

Editing out genetic disorders and/or hereditary diseases to prevent them from ever coming to fruition could also have an enormous impact on reducing the costs of healthcare, effectively helping redefine methods of medical treatment.

It could change lives so that long-term disability care for diseases like Alzheimers and special needs education costs could be significantly reduced or never needed.

Scientists recognized CRISPRs ability to prevent bacteria from infecting more cells and the natural repair mechanism that it initiates after damage occurs, thus having the capacity to halt bacterial infections via genome editing. Essentially, it showed adaptive immunity capabilities.

Its already out there! It has been used for treating sickle-cell anemia and in human embryos to prevent HIV infections from being transmitted to offspring of HIV parents.

IEEE Engineers, like myself, are always seeking to take the fundamental science and expand it beyond the petri dish to benefit humanity.

In the short term, I think that Prime editing will help generate the type of fetal like cells that are needed to help patients recover and heal as well as developing new vaccines against deadly diseases. It will also allow researchers new lower cost alternatives and access to Alzheimers like cells without obtaining them post-mortem.

Also, AI and deep learning is modeled after human neural networks, so the process of genome editing could potentially help inform and influence new computer algorithms for self-diagnosis and repair, which will become an important aspect of future autonomous systems.

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Dwindling tropical rainforests mean lost medicines yet to be discovered in their plants – The Conversation US

Growing up in Tanzania, I knew that fruit trees were useful. Climbing a mango tree to pick a fruit was a common thing to do when I was hungry, even though at times there were unintended consequences. My failure to resist consuming unripened fruit, for example, caused my stomach to hurt. With such incidents becoming frequent, it was helpful to learn from my mother that consuming the leaves of a particular plant helped alleviate my stomach pain.

This lesson helped me appreciate the medicinal value of plants. However, I also witnessed my family and neighboring farmers clearing the land by slashing and burning unwanted trees and shrubs, seemingly unaware of their medicinal value, to create space for food crops.

But this lack of appreciation for the medicinal value of plants extends beyond my childhood community. As fires continue to burn in the Amazon and land is cleared for agriculture, most of the concerns have focused on the drop in global oxygen production if swaths of the forests disappear. But Im also worried about the loss of potential medicines that are plentiful in forests and have not yet been discovered. Plants and humans also share many genes, so it may be possible to test various medicines in plants, providing a new strategy for drug testing.

As a plant physiologist, I am interested in plant biodiversity because of the potential to develop more resilient and nutritious crops. I am also interested in plant biodiversity because of its contribution to human health. About 80% of the world population relies on compounds derived from plants for medicines to treat various ailments, such as malaria and cancer, and to suppress pain.

One of the greatest challenges in fighting diseases is the emergence of drug resistance that renders treatment ineffective. Physicians have observed drug resistance in the fight against malaria, cancer, tuberculosis and fungal infections. It is likely that drug resistance will emerge with other diseases, forcing researchers to find new medicines.

Plants are a rich source of new and diverse compounds that may prove to have medicinal properties or serve as building blocks for new drugs. And, as tropical rainforests are the largest reservoir of diverse species of plants, preserving biodiversity in tropical forests is important to ensure the supply of medicines of the future.

The goal of my own research is to understand how plants control the production of biochemical compounds called sterols. Humans produce one sterol, called cholesterol, which has functions including formation of testosterone and progesterone - hormones essential for normal body function. By contrast, plants produce a diverse array of sterols, including sitosterol, stigmasterol, campesterol, and cholesterol. These sterols are used for plant growth and defense against stress but also serve as precursors to medicinal compounds such as those found in the Indian Ayurvedic medicinal plant, ashwagandha.

Humans produce cholesterol through a string of genes, and some of these genes produce proteins that are the target of medicines for treating high cholesterol. Plants also use this collection of genes to make their sterols. In fact, the sterol production systems in plants and humans are so similar that medicines used to treat high cholesterol in people also block sterol production in plant cells.

I am fascinated by the similarities between how humans and plants manufacture sterols, because identifying new medicines that block sterol production in plants might lead to medicines to treat high cholesterol in humans.

An example of a gene with medical implications that is present in both plants and humans is NPC1, which controls the transport of cholesterol. However, the protein made by the NPC1 gene is also the doorway through which the Ebola virus infects cells. Since plants contain NPC1 genes, they represent potential systems for developing and testing new medicines to block Ebola.

This will involve identifying new chemical compounds that interfere with plant NPC1. This can be done by extracting chemical compounds from plants and testing whether they can effectively prevent the Ebola virus from infecting cells.

There are many conditions that might benefit from plant research, including high cholesterol, cancer and even infectious diseases such as Ebola, all of which have significant global impact. To treat high cholesterol, medicines called statins are used. Statins may also help to fight cancer. However, not all patients tolerate statins, which means that alternative therapies must be developed.

The need for new medicines to combat heart disease and cancer is dire. A rich and diverse source of chemicals can be found in natural plant products. With knowledge of genes and enzymes that make medicinal compounds in native plant species, scientists can apply genetic engineering approaches to increase their production in a sustainable manner.

Tropical rainforests house vast biodiversity of plants, but this diversity faces significant threat from human activity.

To help students in my genetics and biotechnology class appreciate the value of plants in medical research, I refer to findings from my research on plant sterols. My goal is to help them recognize that many cellular processes are similar between plants and humans. My hope is that, by learning that plants and animals share similar genes and metabolic pathways with health implications, my students will value plants as a source of medicines and become advocates for preservation of plant biodiversity.

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Genomic Predictions’ DNA test for embryos claims it can predict diseases and alert parents – Screen Shot

Genomic Predictions DNA test for embryos claims it can predict diseases and alert parents

A New Jersey-based startup developed what it claims to be a genetic test capable of predicting a number of common diseases in embryos. The company, called Genomic Predictions, has been approached by dozens of parents-to-be from across the world in hopes of having the start-up help them weed out embryos more inclined to develop certain diseases later in life, such as cancer and diabetes. Although Genomic Predictions new test is in its infancy, the company has already come under fire by many in the academic and scientific communities, with some depicting the test as both impractical and unethical.

Genomic Predictions has been around for several years now, using various computing technologies, AI and machine learning to research genomes and discover novel ways of predicting phenotypes. Weve always thought that one of the best and earliest applications of this would be embryo selection because we can help families have a healthy child, said Stephen Hsu, the companys co-founder, in an interview for GEN.

Last month, Genomic Predictions finally unveiled a test which it claims can utilise DNA data to predict the likelihood of embryos from an IVF procedure to develop any of 11 types of diseases. As reported by MIT Review, the test, called LifeView, will measure IVF embryos DNA from hundreds of thousands of genetic positions and generate estimates regarding chances of having diseases such as diabetes, heart attacks, and five types of cancer. The test would also alert parents about how likely it is that their child will end up among the shortest 2 per cent of the population or the lowest 2 per cent in intelligence.

Genomic Predictions then hands parents report cards containing the testing results for each embryo so they could implant the ones they deem to be the healthiest out of the batch.

So far, the company reported that 12 clinics around the worldin Nigeria, Peru, Thailand, Taiwan, and the USwill order its new test. The few interested clients are mostly well-off professionals wanting to reduce their childs risk of having diseases that may run in the family. Genomic Predictions first set of clients, for instance, is a gay couple undergoing IVF with a surrogate mother who want to ensure their child wont have breast cancer. Another couple, who have two children with autism, want their third child to be neuro-typical; something they hope the LifeView test could help them achieve.

For the most part, however, clinics are extremely hesitant about ordering this new test, as many scientific experts and researchers voiced harsh criticism of it. It is irresponsible to suggest that the science is at the point where we could reliably predict which embryo to select to minimize the risk of disease. The science simply isnt there yet, tweeted Graham Coop, a geneticist at the University of California, Davis. A research by The Hebrew University of Jerusalem also concluded that attempting to predict the height and intelligence of an embryo is pretty much a futile attempt at this point in time. Others, such as Santiago Munne, an embryo testing expert and entrepreneur, suggest that the great uncertainty that comes with this type of testing would be off-putting for many doctors and client as well as a source for potential disappointment.

And lets not forget about the immense psychological strain such a test can place on children who find out theyve been selected out of a pool of embryos in order to be healthy. What if they do end up developing one of these diseases after all this money had been spent?

While a parents urge to do all in their power to prevent their child from being ill is understandable, this genetic selection process sets us on a very slippery slope. It seems that endeavours such as LifeView constitute a mere hop, skip and a jump away from genetically editing babies, and cater to our growing appetite to design what we perceive to be the perfect human. Naturally, we should support the scientific communitys efforts to find cures and solutions to prevent terrible diseases, but is phenotyping the answer? This approach all but ignores the slew of external and environmental factors that heavily impact someones chances of developing such diseases, including diet, lifestyle, stress, and someones mental state. It could be argued that no less attention should be placed on tackling the latter, as opposed to try and manufacture a flawless human being.

So far, tests like LifeView appeal only to couples using IVF, a process that is long, uncertain, invasive and prohibitively expensive. Some at Genomic Prediction, however, contend that IVF will be the future, claiming that even fertile couples would choose to undergo the process in order to reduce the chances of disease in their children. As such technologies proliferate, we must remain critical and alert of their application and the direction in which it takes our society. Crafting the perfect human and labouring to prevent any flaws in our children could cost us a great deal. Much more than an IVF treatment.

Genomic Predictions DNA test for embryos claims it can predict diseases and alert parents

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Reef Life by Callum Roberts review miraculous and threatened – The Guardian

In August of this year, Gail Bradbrook, a co-founder of Extinction Rebellion, called for the widespread ingestion of psychedelic substances to help bring about a transformation in attitudes to the climate crisis and the living world. The proposal may sound far-fetched, but it has some science behind it. Studies show that, in the right setting, psychedelics can not only be effective against addiction and depression but can also help people feel more connected to nature. Yet the living world of tropical coral reefs surpasses in wonder and beauty anything engendered in the human mind by psychedelics. As the evolutionary biologist Leslie Orgel once said, evolution is cleverer than you are. A reef will convince you that it also has a bigger, stranger and subtler imagination.

Most damage of the last couple of decades has been from manageable stresses like pollution, overfishing and development

There are few better guides to the glories of reefs than Callum Roberts. Reef Life is a vibrant memoir of the joys, as well as the grind, of a research career beginning in the 1980s that has spanned a golden age of coral reef science. It is also a fine introduction to the ecology of reefs and the existential threats they now face. Roberts is well equipped for the task. He is chief scientific adviser to Blue Planet II, and has given us two of the best books in the last 15 years about the ecology of the sea and its fate in human hands: An Unnatural History of the Sea and Ocean of Life.

Roberts revels in the details of life on a coral reef. A mantis shrimp, for instance, has a carapace of mottled green edged with a thin red line like the piping on an iced cake. Its eyes, frosted glass balls on blue stalks, marked with a horizontal line like the slot of a helmet visor, give it an almost supernatural power to see linear and circularly polarised light. This book also addresses the major questions regarding human responsibility and possibilities for change. We live at what is probably the zenith of coral reef evolution in hundreds of millions of years in terms of their diversity and productivity, but human action might bring this all to an end within a few generations: It is an extraordinary position that I still grapple with daily to understand.

Coral reefs are, arguably, lifes greatest miracle. Hugely productive ecosystems in nutrient-poor waters, they harbour a quarter of all marine diversity in less than 0.1% of the oceans extent. On a healthy reef, top predators such as sharks are abundant, while life lower down the food chain appears to be scarce a seeming inversion of the pyramid were familiar with on land, where a vast savannah supports a herd of wildebeest, but only a few lions or leopards. (The solution to the apparent paradox is that life at the lower trophic levels on reefs provides abundant resources for predators but turns over very fast.)

Despite their intense vibrancy, reefs are also vulnerable, both to direct human impacts such as overfishing, pollution and insensitive development, and to indirect impacts of the large-scale combustion of fossil fuels, which result in global heating and changes to ocean chemistry. In the past four decades, three pulses of heat have devastated many reefs around the world, including, in 2016 and 2017, the Great Barrier Reef. The risk to their future is unlike anything they have experienced in millions of years.

There is already a rich literature, and to a lesser extent a filmography, on the threats they face and what, if anything, can best protect them. Among the highlights are John Charlie Verons sober and devastating A Reef in Time, the gripping documentary film Chasing Coral, and Coral Whisperers, Irus Bravermans fluent account of 100 or so interviews with leading scientists and conservation managers. Journalists continue to document how the destruction of reefs impacts on the mental health of researchers, who report ecological grief. Roberts is a humorous, determined expert, who has spent more than three decades trying to come to terms with such issues. As his book begins, he is a fresh-faced student assisting in some of the first detailed studies of coral reefs on the Saudi Arabian coast of the Red Sea. Working in harsh conditions, blundering into embarrassing situations and sometimes exposing himself to danger, he is carried forward by thunderclaps of wonder. A few years later, and now a respected marine biologist, he is assessing the aftermath of the huge releases of oil into the Persian Gulf by Saddam Husseins forces as they fled from Kuwait in the first Gulf war. Remarkably, some of the reefs here among the most northern in the world survive, having escaped the tide of pollution.

Further adventures, from the Caribbean to the Maldives and far beyond, follow. In 2013, Roberts is in Australia supporting scientists and environmentalists who are trying to slow and even reverse the impact on the Great Barrier Reef of the development of new port facilities for the export of coal. By this time, scientists are warning that even a relatively small increase in the global average temperature, let alone the 2 Celsius or more that now looks probable, is likely to have a devastating impact on most of the worlds reefs. Roberts finds himself deployed as part of what turns out to be an effective campaign to change minds regarding the proposed coastal development; by 2015 the opposition Labor Party come to power with a promise to protect the reef. It is poignant to read this in 2019, long after Australian voters have returned a government that does not appear to believe that the climate crisis should be a cause for concern.

I dont know a single coral expert who is not haunted by doubt, Roberts writes. It is already possible to glimpse the most dystopian of futures. But, he stresses, there are hopeful strands. It has been found, for example that some corals can survive in hotter and more acidic waters than was previously thought. Further acclimation and adaptation may be possible in some instances. Genetic engineering to make more heat-resistant corals may be feasible, though controversial. But above all, according to Roberts, there is a role for well-managed marine parks. Most coral reef damage of the last couple of decades has been from manageable stresses like pollution, overfishing and development rather than climate change. Where these pressures are reduced, corals and the endless forms of life they support have a fighting chance.

In a moving penultimate chapter, he describes a visit to Palmyra Atoll in the Pacific, the worlds most isolated reef, and currently among its most intact. Palmyra is part of a huge US conservation zone called the Pacific Remote Islands Marine National Monument. Roberts, with his irrepressible warmth and passion, concludes: Now is the time for action, not mourning. There is everything to play for.

Reef Life: An Underwater Memoir by Callum Roberts is published by Profile (16.99) To order a copy go to or call 020-3176 3837. Free UK p&p over 10, online orders only. Phone orders min p&p of 1.99.

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The Next Olympics Mascot Might Have Been a Mutant Morning Glory – The Atlantic

The 12th-floor apartment of one of Long Island Citys waterfront towers features both spectacular views of Manhattan and a small yet state-of-the-art bioengineering lab, tucked into the spare bedroom. Sebastian Cocioba, a 29-year-old college dropout and self-styled plant hacker, has lived there with his parents for the past decade. And, for the past three years, the condo has also been home to a top secret, gloriously quixotic enterprise: the project to genetically engineer a flower that would serve as the official mascot for the 2020 Tokyo Olympic Games.

When I first visited, on a bright-blue morning in January, Cocioba led me into the kitchen. There, he used the baked-potato setting on the microwave to warm a flask filled with a gelatinous goop of agar, sugar, and fertilizer. Once heated, the mixture loosened up into a free-flowing, straw-colored liquid that smelled, coincidentally, of potato. Meanwhile, Cocioba opened the fridge, reaching into a drawer divided in halfdeli meats and cheese on the left, hotel-shampoo-size bottles of chemicals on the rightto retrieve two vials of plant hormones. Look, we eat these in pretty decent amounts in salad, Cocioba said, in response to my raised eyebrows. My parents have kind of gotten used to the whole concept of this by now.

Down the hall, in the lab, Cocioba assumed the role of patient tutor, while I switched on the laminar flow hood, gloved up, and used a pipette to transfer each hormone, in a carefully measured ratio, to the agar jelly. My task for the day was to insert a small genetic sequence into a white petuniaa small but important step toward the larger goal. Our tool was a plant pathogen known as Agrobacterium tumefaciens, which hijacks its hosts by sending out small packages of membrane-wrapped DNA capable of inserting themselves into the other plants genome.

Cocioba and I prepared the petunia for infection: he by stripping off some leaves the day before and leaving them to sterilize overnight in a weak bleach solution, I by using a hole punch to cut out dozens of neat circles of leaf tissue that I then tweezered gently into petri dishes filled with our cooled, yellow jelly. The freshly injured leaves emitted a chemical distress signal that was undetectable to me but that Cocioba assured me would act as a red rag to the bullish Agrobacterium.

The genetic sequence we were hoping to infect them with was a probe, capable of finding and binding to a target sequence in the petunias DNA, and it held a tail of green fluorescent protein that would only unfold enough to glow once a successful bond had formed. Cocioba had ordered the probe online and stored the vial, containing a single clear droplet filled with enough genetic material for 50-odd experiments, in the freezer, beneath a bottle of vodka and some tater tots, until he was ready to add it to our batch of Agrobacterium.

Dosing the plant tissue with hormones was a warm-up for the main event: Together, the chemicals would return chunks of adult planttissue that had already become root, stalk, or leafback to an embryonic state. Post-infection, Cocioba would use the same hormones, in different ratios, to organize the cells in each proto-plant disc back into the constituent parts of a seedling that he could cultivate, and that, if our experiment was a success, would emit an eerie greenish glow under a fluorescent microscope.

In October 2015, the interaction designer Kevin Slavin was in Tokyo, meeting with senior executives at Mori Building Company, Japans largest commercial landlord. Slavin is a skinny geek who trained as an artist; developed one of the first location-based phone games, Pokmon Gos predecessor; and then founded the Playful Systems lab at MITs Media Lab. He was in town to present the results of a successful collaboration with Mori that had used bees housed atop the companys properties to map the citys microbiome. (The bees functioned as distributed surface-sampling devices, and by collecting their waste from the hive every week and sequencing the DNA found within it, Slavin was able to conduct a microbial census on a neighborhood-by-neighborhood basis.)

The conversation turned to the future. Masa Ogasawara, Moris sphinxlike executive managing officer, asked whether Slavin had any ideas for a project for the Tokyo Olympics.

Slavin, who had spent a considerable amount of time in Tokyo for the bee project, had noticed the citys preparations, and found them vaguely depressing. I actually love the Olympics, he told me. But I love what they are intended to be, and I really respond badly to the crass commercial qualities of it. Meanwhile, to sequence the microbial DNA collected by his bees, he had also been spending time with the computational biologist Elizabeth Hnaff, and as he began to learn about new gene-editing techniques such as CRISPR, he realized that engineering life was no longer science fictionit was the imminent future.

As he reflected on what he disliked about the Olympicsthe tchotchke-choked monetization that accompanies an otherwise stirring display of human effort, teamwork, and excellenceSlavin wondered what its opposite would be. A true Olympic mascot, he felt, should be a source of delight and wonder and beauty, and actually add something to the planet instead of just ending up in a landfill somewhere.

Slavin imagined designing a new form of life, to be collectively grown and given awayperhaps a tree, genetically modified so that its leaves expressed Olympic colors. He told Ogasawara that he had an idea, but that there was no way Mori would be bold enough to do it. This, unsurprisingly, was like catnip to the powerful executive, and the company quickly signed on to support the creation of the worlds first genetically modified Olympic mascot.

When Slavin got back to New York and described his vision to actual biologists, including Hnaff, they gently pointed out that any plan that involved growing a tree from an embryo in five years, let alone engineering an entirely new variety and then propagating it, was hopelessly ambitious. A genetically modified flower, on the other handwell, that might just work.

The first Olympic mascot was Waldi, a striped cartoon dachshund who made his debut in Munich, at the Summer Games of 1972. Designed by Otl Aicher, better known for the Lufthansa logo, it is also the most tasteful mascot to date. Londons 2012 one-eyed Mr. Blobby lookalike, Wenlock, is probably the fields nadir, but the brief to represent the host countrys cultural heritage in a festive way and appeal to a younger audience has rarely resulted in design excellence. The problem is that all these things are done by consensus, says Paola Antonelli, a senior curator of architecture and design at New York Citys Museum of Modern Art. Did you see the overweight bald eagle from Los Angeles?

The Tokyo Games, by contrast, were off to an aesthetically pleasing start. The official logo, unveiled in April 2016, consisted of 45 dark-blue rhomboids arranged into a wreath. Officially named Harmonized Checkered Emblem, it is a minimal masterpiece designed by the artist Asao Tokolo, who uses a ruler and compass to create repeating patterns. In his studio in Tokyo, Tokolo sketched a quick diagram to show me how the logos color was derived from the angles of three rectangular forms100, 86, and 50, which, when translated to the cyan, magenta, and black of a printing press, produce the same deep indigo traditionally worn by samurai.

This checkerboard pattern is called ichimatsu in Japanese, after an Edo-era kabuki heartthrob, Sanogawa Ichimatsu, who habitually performed in a patterned costume. Mathematicians have calculated that the logos rhomboids can be rearranged into half a million new patterns, Tokolo said. He showed me a printout of a paper analyzing his logo, titled On the Enumeration of Chequered Tilings in Polygons. This combination of rule-bound repetition and near-infinite variation makes the logo into a universal code, he told me, opening his laptop to play Pachelbels Canon as an illustration. This way, he said, its shareable, transferrable, and transformablelike music, math, and, I couldnt help but think, DNA.

As soon as he saw Tokolos logo, in early 2016, Slavin knew that the Olympic-mascot flower should be engineered to have an indigo-and-white ichimatsu pattern on its petals. At the same time, Hnaff suggested using the morning glory, a flower she lovesshe has a tattoo of a purple morning-glory vine covering the entire side of her bodyand that she knew, from time spent working in Japan, held a particular significance in the country. You see it growing in little postage-stamp gardens in the older neighborhoods of Tokyo, she told me. And then you realize theres morning glories everywhere, in illustrations and artwork and all the lovely printed fabrics.

In much of the rest of the world, the twining vine is seen as a weed, even a nuisanceits touch-sensitive tendrils help it climb walls and facades, hooking into tiny cracks and turning them into fissures. But in Japan, asagao, which translates to morning face, is a cultural icon, its imperial-blue, trumpet-shaped flowers symbolizing high summer in the same way that cherry blossoms signify the arrival of spring.

The species is thought to be native to Central America, where the psychoactive alkaloids found in the seeds of some varieties were used in Aztec rituals, but according to Reiji Iwabuchi, a scholar who has curated a series of exhibitions on morning glories at the National Museum of Japanese History, the flowers were brought to Japan from China in the ninth century. The earliest Japanese mentions of the plant cite its usefulness as a laxative, he told me, and it is pictured in a set of scrolls from 1164, preserved at the Itsukushima Shrine.

In his dark, book-lined office on the campus of Gakushuin University, just steps from the neon excess of Shinjuku in Tokyo, Iwabuchi showed me a series of reproductions illustrating the next phase in the morning glorys rise to popularity. By the early 1700s, Japans doors had been closed to the world for nearly a century. In Tokyo, then known as Edo, but already one of the largest cities in the world, culture flourished and a distinctly Japanese relationship with nature, as well as the craft of expressing its essence in miniature, was refined. Bonsai trees became popular, as did suiseki, or the art of selecting and displaying stones that represent larger landscapes, such as mountains, canyons, or coastlines. Flower vendors walked the streets, selling chrysanthemums and camelias, while feudal lords rewarded their favored retainers with potted plants.

Iwabuchi pulled out a print of a gorgeous gilded screen from the mid-18th century. The artist, Jakuchu Ito, is known for his depictions of chickens, and this print showed a rooster perched on one leg, head turned to face his own dazzling black-and-white tail feathers. In the background are a handful of sunflowers and, woven through them, a spatter of morning glories. Instead of the standard solid blue-purple, the flowers are as variegated as the roosters own plumagethere are solid white flowers, but also white flowers speckled with blue, or sporting a series of blue wedges of different sizes. This, Iwabuchi told me, is the first record of a floral phenomenon that was soon to sweep the city: the cultivation of henka asagao, or mutant morning glories.

The first morning-glory craze lasted 30 years, beginning in 1800, and infected all levels of society. The trend was for differently colored and patterned flowersspeckled, striped, albino, half-and-half, pink, maroon, and even a creamy-yellow phantom morning glory that modern breeders are still unable to reproduce. Monks and samurai raised thousands of morning glories in their gardens as a side hustle, selling regular purplish-blue flowers to the common people and sought-after mutants to wealthy collectors. Anthologies cataloged the varieties, naming each mutation after literary characters; woodcuts depicted shoppers carrying potted morning glories back from shrines, as well as morning-glory viewing parties in late summer. One kabuki actor, who dressed in a morning-glory print and went by the stage name Asagao Senbei, or Morning Glory Rice Cracker, had an entire routine that involved starting vigorous fights, then quickly fading and losing, in the same way that a morning glory blooms at dawn, only to shrivel up by the time lunch is over. But then, Iwabuchi said, for reasons that remain hard to discern, public interest shifted, and the Japanese sacred lily and painted fern were suddenly all the rage.

In the 1850s, another chance mutation birthed a second, mini-boom: This time, growers competed to produce morning glories with curling, ribbonlike petals as opposed to the standard trumpet, or with leaves that forked like a snakes tongue. Mutant morning glories became a status symbol, Iwabuchi explained, and flower nerdsmorning-glory maniacscompeted between themselves to select and maintain the most spectacular deformations.

The final wave of morning-glory popularity came in the 1870s, after the arrival of American gunboats had forced the country to open up. In a wave of nostalgic, nationalistic sentiment, social clubs devoted to raising mutant morning glories formed, keeping many rare strains alive. Iwabuchi showed me a black-and-white photo from 1910, showing what he called a nerd gardenthousands of seedlings, growing in pots under netting in preparation for the annual morning-glory fair in the Tokyo suburb of Iriya.

Since his first exhibition on the subject, 15 years ago, Iwabuchi has seen a renewal of interest in the flower. Japanese schoolchildren grow the basic morning glory as a summer project in elementary school, making it a piece of nature that all the countrys citizens have some connection to, but mutant sales have recently become a major source of revenue for the museum. I believe we are at the start of the fourth boom, he said.

At this point, the idea of a mutant morning glory, engineered to express the recombinant code of the official Olympic logo, began to assume an almost unbearable rightness. It blended Japans unique culture and history with the latest technology. The fleeting symbolism of the flower even embodied something of the magic of the Olympicsan event that briefly captures the worlds attention every four years, before disappearing again.

Meanwhile, those involved in the project found something that spoke to their own, deeper desires. For Slavin, it was this idea that designers could make a living organism rather than a product, something that would add to the world rather than extract more of its resources. For Hnaff, the projects almost whimsical goal created an opportunity for a more meaningful conversation about the rights and wrongs of genetic engineeringa less fraught way to think through what it means for humans to have user-level privileges over other species genetic identity. In a world where proponents of genetically modified organisms say they are needed to solve world hunger, and their critics say they are being used by corporations to perpetuate inequality, she explained, oftentimes, the conversation about the technique and the conversation about the goals get kind of muddied.

For Mori, the project captured something of the subtle Japanese conception of the relationship between humans and nature. Japan is the largest industrialized country that still actively practices an indigenous, animist religion, in which nature does not belong to humans, but vice versa. We have always designed life, Jun Fujiwara, Moris director of special projects, told me, pointing out that the foods and drinks most central to Japans identitysake, miso, nattorely on microbial communities that are a hybrid of nature and culture. From this perspective, perhaps a genetically modified morning-glory Olympic mascot could be a kind of Shinto GMOan organism that embodied not only deep respect for the astonishing ingenuity and beauty of the natural world, but also a sense of necessary awe at the craft with which humans can shape it.

And, finally, for Sebastian Cocioba, the plant hacker that Hnaff brought in to work on the project full-time, the morning glory offered a step toward his life goal of becoming a flower designer. As a teenager, Cocioba funded his studies by flipping Home Depot orchids: When his local store threw out plants that had ceased to flower, Cocioba retrieved them, dosed them with blue light and hormones, and sold them back. He built his lab by buying broken equipment on eBay and fixing it. This project promised a salary and a chance to make something that would be seen on the world stage.

In early 2016, with the flower and pattern decided and Mori funding secured, the teamSlavin, Hnaff, and Cociobagathered around Cociobas parents dining table to brainstorm. In their excitement, they used a blue whiteboard marker to scrawl diagrams, sketches, and chemical formulas all over the white kitchen cabinets, where the drawings remain to this day.

As Hnaff and Cocioba broke it down for Slavin, the flower presented two distinct challenges: making a white morning glory with the ability to produce indigo blue, and then manipulating the expression of that color over time. As it turns out, true blue is actually quite rare in flowers, for evolutionary reasons: Pigments initially evolved to protect organisms by absorbing ultraviolet light, and tweaking those metabolic pathways to reflect more blue and absorb reds at the other end of the spectrum presents an almost insurmountable biochemical challenge. Most blue flowers are purple-tinged, and even hydrangeas and cornflowers cannot achieve a true blue without some additional help from acidic or magnesium-rich soil.

Whats more, the genetically modified version of the multistep process by which plants naturally transform pigments from red to purplish-blue has been patented by Suntory, a Japanese whiskey company. In 2004, Suntory partnered with Florigene, an Australian genetic-engineering firm, to create what it claimed was the worlds first true-blue rose. It drives me nuts, because its purple, Cocioba told me. (The rose technically contains blue pigments, but appears indisputably lavender-colored in press images.) Cociobas proposed solution was to avoid the nine genes required to produce purplish-blue in plants altogether. Instead, he planned to engineer a white morning glory into which he would insert a single gene borrowed from coral, where it would express an intense ultramarine protein.

Typically, a petals cells grow in an unbroken line outward, which is why two-tone flowers usually feature either landing strips or radial, halo effectsthe color that each cell expresses at the center is the color it will express along its entire arc of growth. To create a checkerboard pattern, Cocioba and Hnaff would have to engineer a switch of some sort, so that they could flick the blue protein on and off at regular intervals within the four-hour window during which morning-glory petals develop from bud to flower.

Luckily, the morning glory had already mastered that trick on its own: Think of the blue-speckled white flowers in the background of Jakuchu Itos rooster painting. Such mutations are due to transposons, mobile DNA sequences capable of hopping into, say, the genes that synthesize blue pigment, temporarily disrupting their ability to function and creating a white patch, before jumping out again, at which point the color returns. Every living thing has these jumping genes, but they are particularly active in morning glories, where scientists theorize that selection, both by pollinators and, latterly, humans, has favored the resulting diversity.

Hnaffs earlier research had focused on transposable elements, and on Cociobas parents freezer drawer, shed illustrated the idea of a built-in on/off mechanism using a series of arrows and squiggles. The idea was, Well, you know, if this switch already exists, then maybe we can just tweak its activity and decide when it goes on and off, she said. Not all the natural triggers for a gene jump are known, but some are well described, including an insect attack, water stress, and temperature change. Standing in front of the fridge, pen in hand, Hnaff suggested putting their prototype plants in an oven and setting the thermostat to oscillate as the flower developed. That way, they could figure out the exact pigment on/off sequence needed to make a checkerboard, and then find a way to genetically hard code that timing into the final flower, Hnaff explained.

The science seemed ambitious but not impossible. Hnaff did a literature review, and saw that morning glories had been successfully engineered using Agrobacterium and cultured in a lab. She even found descriptions of engineered pigment transformations, although none included the rapid on/off oscillation this design would require. She consulted with other biologists, who agreed: feasible, potentially even in a quick time frame. Slavin emailed a photo of his kitchen-cabinet flower sketch to a friend and asked him to render it in Photoshop, then built a Keynote presentation. Cocioba ordered DNA, reagents, and a packet of imperial-blue morning glory seeds from Japan. Through an intermediary, Mori helped set up a series of meetings with representatives from the Office for the Promotion of the Tokyo 2020 Olympic and Paralympic Games, as well as other government officials.

The enthusiasm for the flower was palpable. Slavin, who does not speak Japanese, remembers one man turning to the guy next to him and muttering something that included the words fast money. They were like, We understand that this is speculative and we respect that, Slavin said. We know you might not make it. So well give you a year. Is that fair? And were like, Yep, totally fair, totally doable.

A few months in, the team confronted an issue. Cocioba had never worked with morning glories, so his first step was just to get it to grow in tissue culture, like our hole-punched petunia leaves. For the first two months, I did all of the things, he said. I threw the entire book at it, trying to get it to regenerateand no dice.

Hnaff went back to the papers that described morning-glory cultivation in tissue culture and discovered a note explaining that the morning glory was missing the one gene that would allow its leaves and stem to return to an embryonic state in response to plant hormones. Instead, the authors wrote, the only morning-glory tissue that will regenerate in culture is an actual immature embryo. Suddenly, Cocioba had an urgent need for seed.

So I started growing morning glory like it was weed, Cocioba said. He rented an artists studio a few blocks from his parents condo in Long Island City, bought grow lamps and metal racks from IKEA, and threw all the chemicals he could at the baby plants to get them to flower fast. And then, nearly three months later, once they had flowered, Cocioba had to figure out how to pollinate his morning glories so that they would set seed. I found a company online that sells dead bees on sticks, he said. They work wonderfully, but let me tell you, manually pollinating thousands of flowers took for...ever.

When Cocioba finally harvested a seedpod, it took him two hours of surgery to get an embryo out. It was half a millimeter long, he said, showing me a photo on his phone of a greenish dot. If you pinch it, it dies; if you look at it funny, it dies; if a butterfly farts in Russia, it dies.

The morning glory was not the only recalcitrant player. Later that year, Kevin Slavin left his faculty position at the Media Lab, and the accounts-payable department at MIT proved reluctant to funnel Moris funds to a 20-something in Long Island City. Back in Tokyo, Mori was handling the project as it might manage any business initiative: with an insistence on timelines, check-ins, reports, and deliverables. It was planned like a construction project and funded like a government project, meaning the money came in a year later, Cocioba saidleaving him wrestling with an uncooperative flower, working on other projects to pay bills, and missing deadlines left and right.

He and Hnaff made an executive decision: They would prototype using petunia, which grows happily in culture and flowers faster. To try to speed things up, Hnaff spent weeks sequencing a white and a purple petunia and assembling their genomes, so that Cocioba would have an accurate road map to work with. Its borderline biblical, the level of precision that we have on these two plants, Cocioba said.

In spring 2017, with no flower in sight, the Japanese Olympic Committee announced a mascot design competition. Schoolchildren were invited to vote for their favorites, in a bid to make the Tokyo Games seem participatory and transparent following repeated accusations of graft. The resulting mascot, Miraitowa, is a big-eyed cartoon character that looks like a blue-and-white-checked cartoon kitten. According to the mascot-selection panel, he is imbued with energy that will cheer up and cheer on the athletes, although critics have described him as a Pokmon refugee. Just as Slavin had hoped to avoid, factories in China are already churning out Miraitowa plushies by the million. Miraitowa T-shirts, baseball caps, collectible pins, and stuffed dolls are expected to bring in about 14 billion yen in revenue for the Games organizers.

With the mascot decided, Takeo Hirata, head of the Office for the Promotion of the Tokyo 2020 Olympic and Paralympic Games, told Slavin that his genetically modified morning glory could instead become an Olympic emblema new category of Olympic symbol. Hirata suggested that the checkerboard flower could replace posters and banners in some places, and that the Japanese government could still distribute it to all public primary schools in spring 2020. Which meant that the pressure from Mori continued, with the company sending Jun Fujiwara to New York City to visit Cociobas apartment lab on a regular basis.

By now, Slavin was distracted by the demands of a new job. Meanwhile, after finding that, for months, Fujiwara had removed her name from reports shed prepared and left her off update emails, Hnaff had distanced herself from the project. The final straw came when Mori arranged to bring Cocioba and Chris Mason, the Cornell geneticist in whose lab Hnaff had been a postdoctoral student when the project began, to Tokyo to present the groups research. Though both Cocioba and Mason considered Hnaff the projects principal scientist, she didnt hear about the trip until Cocioba called her to see where she was staying. I wasnt even contacted about it, she said. At that point, disgusted and demoralized, she was done. (Fujiwara, when asked about his reasoning, blamed limitations of time and space.)

In October 2017, after their presentation in Tokyo, Mason and Cocioba were drinking beer at the Park Hyatt bar, better known as the setting for a scene in the movie Lost in Translation, when Mason received an email from Fujiwara requesting that he present an update on the flower project to Moris president the next day.

Until that point, Masons involvement in the project had largely been limited to providing access to computing power, as well as managing funds following Slavins departure from the Media Lab. Scrambling, Mason did something no one on the team had done before: a Google Image search for checkerboard-pattern flower. Astonishingly, one came upthe snakes head fritillary. Cocioba then entered the plants scientific name, Fritillaria meleagris, into a scientific database and told Mason that it has one of the largest genomes on the planet, at about 156 billion base pairs to the human genomes paltry 3 billion.

As soon as I told Chris that, his eyes lit up, because he loves superlatives, Cocioba said. Hes like, now I have a purposewell sequence it! A chunk of the Mason Labs funding comes from NASA, and somehow, over the course of that evening, Masona creative thinker who has also written a short volume of genetic poetrydecided that the process that produced a checkerboard pattern in the snakes head fritillary could serve as a model for the mechanisms that cause changes to an astronauts DNA in space.

The next day, Masons PowerPoint contained NASAs logo and a photo of the flower, grabbed from the Brooklyn Botanic Gardens website. Slavin received a copy in an email update from Mason, in which the projects goal is described as astronaut protection, and Slavin is listed simply as an adviser. This is out of nowhere, Slavin recalled. NASA? What? Im like, How far up the river has this been sold, by how many people?

A few hours west of Tokyo by bullet train lies the Japanese National Institute for Basic Biology. When I visited, one morning in March, a slight, baby-faced scientist named Atsushi Hoshino loaned me a pair of orange Crocs and led me into his greenhouse. Inside, spilling over wire racks and tangling together, was a jungle of mutant morning gloriesnearly 200 in total, he told me, each one unique. An enormous deep-burgundy flower with a white center almost sparkled, its petals velvety under the lamps; in the corner were white flowers, each with one or two wedges of pink, and on the rack above, deep-blue flowers with rays of purple.

I screen 4,000 baby plants each year to discover new mutants, he told me. The normal morning glories end up in the incinerator; the mutants go into the greenhouse. In his lab, next door, 800 seedlings were growing in trays under lights, each just a couple of inches tall and too young to flower. Hoshino showed me his only hope from this latest batch; its sole leaf was split down the middle, half lime green and half emerald. A transposon has disrupted the gene for chlorophyll, he explained, with a shy smile.

Mutant morning glories have been at the center of Japanese genetic research for more than a century, Hoshino told me. The 19th-century samurai and monks who competed to breed the most spectacular new mutations had no idea what a gene was, let alone one that jumped. But morning glories were the topic of the first bulletin of the Japan Breeders Association, in 1916, and after the Second World War, the Japanese government collected all the mutants it could find from hobbyists and founded a national research center. Since then, by analyzing these mutants, Japanese researchers have discovered many of the genes that determine flower and leaf shape, color, and pattern.

As a doctoral student, Hoshino wanted to study rice, in order to develop useful improvements for Japanese farmers. In my lab, there was a better student, and she chose the rice project, he told me. So my boss gave me mutant morning glories for my thesis topic. Decades later, Hoshino feels that he was the lucky one. There are hundreds of possibilities for patterns, he said. We only fully understand a few. He pointed to a blue flower with a white halo at its edge. Why is the silencing expressed only at the margin? he asked. No one knows. Although he used to think of genes as stable, heritable sets of instructions, morning glory has taught him to see them as a dynamic system, whose shifts we have yet to comprehend. We need mutant morning glories to teach us how this works, he said.

Back in New York City, Cocioba unknowingly echoed Hoshinos words. In the end, morning glory taught us that we know nothing about morning glory, he said. In October 2018, in an abrupt email, Mori pulled the plug on the project, but Cocioba continued working on his petunia prototype on evenings and weekends. The experiment we did together was a test of his genetic guide; it was the final step before he attempted to insert his new blue gene from coral. With Mori out of the picture, Hnaff was once again involved, and together they were looking for funding.

The morning-glory mascot had taught Hnaff something, too: how not to manage a project. Really, the tragic flaw was the hubris of thinking that we could deliver a new plant on a human schedule, she told me. Already, she said, the project had yielded enough in the way of new knowledge for at least a couple of papers. If, in the future, Cocioba succeeds in turning his white petunia blue, the economic reward could be substantial: Experts have estimated the value of a true-blue rose at many millions of dollars. If they manage to design a switch to turn the gene producing that color on and off during the buds development, the impact will go far beyond horticulturealthough Cocioba warned me that, once humans have the ability to create petal patterns on demand, we should expect to see Nike swooshes and McDonalds arches on our flowers shortly thereafter.

The morning-glory mascot project was, unquestionably, a failure. Kevin Slavins ambitious vision of a beautifully designed plant, whose seeds could be given away to visitors and raised in pots by schoolchildren on the balconies and in the alleyways of Tokyo, will not become realityif it ever could have, given the constraints on releasing gene-edited organisms. From a cultural perspective, it was a clusterfuck, Slavin concluded. From a scientific perspective, it may yield something thats more important than anything we could have ever imagined.

And then Slavin told me another story, about the poet John Giorno. In 1970, Giorno worked with MoMA to create an installation called Dial-a-Poem, in which visitors were invited to call a number to hear one of 50 poems. They had to figure out how to do itthey had to hook up tape recorders and solve a bunch of difficult problems, Slavin said. And they did, and that idea led to a multibillion-dollar industry of 1-800 numbers.

Slavins point was that when designers and artists flirt with science and technology, they can unlock new ways of thinking, from which new ways of being and doing emerge. In the case of Dial-a-Poem, the unexpected consequences were rather banal, Slavin said. But, in this case, it might be something great.

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The Next Olympics Mascot Might Have Been a Mutant Morning Glory - The Atlantic

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