Tag Archives: synthetic biology

Our Biggest Weakness: Weak Biodefenses + Malicious Viruses

The coronavirus that has killed over 180,000 people worldwide was not created with malice. Analysis of its genome suggests that, like many new pathogens, it originated by natural selection rather than human design. But …“Covid-19 has demonstrated the vulnerability of the US and global economy to biological threats, which exponentially increases the potential impact of an attack,” says Richard Pilch of the Middlebury Institute of International Studies. In theory, bioweapons are banned. Most countries in the world are party to the Biological Weapons Convention (BWC) of 1975, which outlaws making or stockpiling biological agents for anything other than peaceful purposes. But some countries probably make them secretly, or keep the option close at hand. America accuses North Korea of maintaining an offensive biological-weapons programme, and alleges that China, Iran and Russia dabble in dual-use biolgical research (for peaceful and military usage) research. Toxins like ricin have also been bought and sold on shady recesses of the internet known as the dark web.

Germ warfare briefly rose to prominence in September 2001, when letters laced with anthrax spores were mailed to American news organisations and senators, killing five people. That was a wake-up call. Public health became part of national security. BioWatch, a network of aerosol sensors, was installed in more than 30 cities across America. But in recent years threats from chemical weapons, like the sarin dropped by Syria’s air force and the Novichok smeared on door handles by Russian assassins, took priority.

Though the Trump administration published a national biodefence strategy in 2018, it shut down the National Security Council’s relevant directorate and proposed cuts to the laboratories that would test for biological threats. Funding for civilian biosecurity fell 27% between fiscal years 2015 and 2019, down to $1.61bn—less than was spent on buying Black Hawk helicopters.

Yet many pathogens used as weapons tend to differ from respiratory viruses in important ways. Those like anthrax, caused by bacteria which form rugged and sprayable spores, but do not spread from human to human, have the advantage of minimising the risk of rebound to the attacker. With the notable exception of smallpox—a highly contagious and lethal virus that was eradicated in 1979 but preserved by the Soviet Union for use against America (but not Europe), and now exists only in two laboratories, in America and Russia—most biological weapons would therefore have more localised effects than the new coronavirus.

Even so, the slow and stuttering response to the pandemic has exposed great weaknesses in how governments would cope…demonstrating that every part of public-health infrastructure is either broken or stretched to the max. The centrepiece of America’s biosurveillance programme, a network of laboratories designed for rapid testing, failed, says Mr Koblentz, while the national stockpile of face masks had not been substantially replenished in over a decade. Would-be attackers will take note.

In 2016 American intelligence agencies singled out genome editing as a national-security threat for the first time. Two years later a major study by the National Academies of Sciences, Engineering, and Medicine warned that synthetic biology, a potent set of methods for tinkering with or creating organisms, could, in time, be used to re-create viruses like smallpox or make existing pathogens more dangerous, such as resistant to antibiotics. In 2011 Dutch and Japanese scientists said that they had created a version of bird flu that could be transmitted between mammals by the respiratory route—an announcement that prompted the Netherlands to treat the relevant academic papers as sensitive goods subject to export controls.

In January 2020 Canadian scientists funded by an American biotech company used synthetic DNA from Germany to synthesise a microbe closely related to smallpox, indicating the ease with which it could be done. “If a potential bad actor pursues a weapons capability using sars-cov-2, the virus is now attainable in laboratories all around the world, and blueprints for assembling it from scratch have been published in the scientific literature.”

 The trouble is that biodefence has evolved slowly, says Dan Kaszeta, a former biological weapons adviser to the White House. Compact devices that can detect chemical threats and warn soldiers to don a gas mask have long been available. “That doesn’t exist for anthrax or any of the other aerosol pathogens,” says Mr Kaszeta. “Telling the difference between an anthrax spore and a bit of tree pollen is not something you can do in a couple of seconds.”

Excertps from Biodefence: Spore Wars, Economist, Apr. 25, at 19

How to Engineer Bacteria to Search for Underground Chemical Weapons: DARPA

U.S. military researchers asked in 2019 two companies to develop new kinds of biological sensors that can detect underground disturbances or the presence of buried chemicals or weapons.

Officials of the U.S. Defense Advanced Research Projects Agency (DARPA) in Arlington, Va., are looking to Raytheon BBN Technologies, and Signature Science, for the BioReporters for Subterranean Surveillance program.  This project seeks to use indigenous and engineered organisms to sense changes of interest to military commanders in natural and built environments. Raytheon BBN and Signature Science won separate $1.6 million contracts for the Subterranean Surveillance progam.

The two companies will perform laboratory research and proof-of-concept demonstrations of biological sensing systems in well- controlled field tests that take advantage of recent advances in microbial science and synthetic biology to develop biological sensors, signal transducers, and reporters that can reveal subterranean phenomena at a distance.  Bio Reporters should be able to sense a phenomenon at least one meter below the surface, propagate a signal to the surface within seven days, and be continuously detectable on the surface at a distance of 10 meters over the subsequent seven days.

DARPA researchers want Raytheon BBN and Signature Science experts to take advantage of the extensive biological networks that exist underground to monitor large areas to increase the military’s ability to detect subterranean events without the need for precise coordinates.

Excerpts from John Keller, Researchers eye new biological sensors to to detect underground objects like buried chemicals and weapons, https://www.militaryaerospace.com,  Nov. 6, 2019

In more detail  Signature Science and its partner, the Texas A&M University Center for Phage Technology, aim to leverage modern and synthetic phage biology and the straightforward molecular genetics of the harmless soil bacterium Bacillus subtilis to generate a new platform to recognize and report on specific chemical threats underground. The Spore-Phage Amplified Detection (SPADe) method, potentially extensible to explosives, radiation or physical disturbance sensing, seeks to substantially advance currently used techniques which rely heavily on manual soil testing. 

Modernize or Die: Bio-Engineered Food

China is betting that CRISP technology*can transform the country’s food supply.  China also expanded its efforts beyond its borders in 2017, when the state-owned company ChemChina bought Switzerland-based Syngenta—one of the world’s four largest agribusinesses, which has a large R&D team working with CRISPR—for $43 billion. That was the most China has ever spent on acquiring a foreign company, and it created an intimate relationship between government, industry, and academia—a “sort of a ménage à trois” that ultimately could funnel intellectual property from university labs into the company, says plant geneticist Zachary Lippman of Cold Spring Harbor Laboratory in New York.

Chinese leaders “want to strategically invest in genome editing, and [by that] I mean, catch up,” says Zhang Bei, who heads a team of 50 scientists at the Syngenta Beijing Innovation Center…China may one day need CRISPR-modified plants to provide enough food for its massive population….    China needs to resolve how it will regulate CRISPR-engineered crops—a divisive issue in many countries. In a 2018 decision that rocked big agriculture, a European court ruled that such crops are genetically modified organisms (GMOs) that need strict regulation. In contrast, the U.S. Department of Agriculture (USDA) exempts genome-edited plants from regulations covering GMOs as long as they were produced not by transferring DNA from other species, but by inducing mutations that could have occurred naturally or through conventional breeding.  Chinese consumers are wary of GM food. The country strictly limits the import of GM crops, and the only GM food it grows are papayas for domestic consumption. But for CRISPR, many plant researchers around assume China will follow in the United States’s footsteps…

For Corteva, Syngenta, and the other two big ag companies—BASF and Bayer (which acquired Monsanto last year)—the long game is to use CRISPR to develop better versions of their serious moneymakers, the “elite” varieties of a wide range of crops that have big commercial markets. They sell dozens of kinds of elite corn seeds—for example, inbred strains that consistently have high yields or reliable resistance to herbicides. Creating the genetic purity needed for an elite variety typically takes traditional breeding of many generations of plants, and CRISPR is seen as the cleanest way to improve them quickly. The earlier methods of engineering a plant can lead to unwanted genomic changes that must be laboriously culled…

Syngenta sees CRISPR-modified corn as a big opportunity in China, which grows more hectares of corn than any other crop. Yields per hectare are only 60% of those in the United States because corn ear worms often weaken Chinese crops. A fungus thrives in the weakened plants, producing a toxin that makes the resultant ears unfit for animal feed. As a result, China must import a great deal of corn. (According to USDA, 82% of U.S.-grown corn has been engineered to have a bacterial gene that makes it resistant to ear worms.)…“Syngenta is putting a lot of emphasis to grow in China to become the leading seed company. The China market as a whole, if it modernizes as the U.S. has modernized, can be as big as the U.S. market.”

Jon Cohen, To feed its 1.4 billion, China bets big on genome editing of crops, Science Magazine, Aug. 2, 2019

* Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9.

Fixing the Earth: De-Extinction

Is extinction forever? Efforts are under way to use gene editing and other tools of biotechnology to “recreate” extinct species such as the woolly mammoth and the passenger pigeon. Could such “de-extinction” initiatives aid conservation by reviving species lost to habitat destruction and climate change?…. These are some of the questions addressed in Recreating the Wild: De-extinction, Technology, and the Ethics of Conservation, a new special report of the Hastings Center Report.

Advances in biology have revealed the ways the environment influences species’ genomes. Even if scientists could produce creatures with DNA identical to that of extinct species, different environmental pressures would alter their genomes in novel ways, raising the possibility that those creatures would differ from the extinct species…

Many scientists believe that although the maintenance of biodiversity benefits ecosystems, changes to the environment could make the reintroduction of extinct species difficult—possibly even ecologically disruptive. …Several commentators in the report raise the concern that the notion that extinct species might be “brought back” could weaken efforts to prevent extinctions. “By proposing that we can revive species through modern technology, we give the impression that species are ‘throwaway’ items,” write Robert DeSalle, a curator at the American Museum of Natural History’s Sackler Institute for Comparative Genomics, and George Amato, director of the conservation genomics program at the institute.

Excerpt from Recreating the wild: De-extinction, technology, and the ethics of conservation, https://phys.org/news/, Aug. 2017

Unsafe Genes: DARPA

DARPA created the Safe Genes program to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse. Today, DARPA announced awards to seven teams that will pursue that mission, led by: The Broad Institute of MIT and Harvard; Harvard Medical School; Massachusetts General Hospital; Massachusetts Institute of Technology; North Carolina State University; University of California, Berkeley; and University of California, Riverside. DARPA plans to invest $65 million in Safe Genes over the next four years as these teams work to collect empirical data and develop a suite of versatile tools that can be applied independently or in combination to support bio-innovation and combat bio-threats.

Gene editing technologies …[can] selectively disable cancerous cells in the body, control populations of disease-spreading mosquitos, and defend native flora and fauna against invasive species, among other uses. The potential national security applications and implications of these technologies are equally profound, including protection of troops against infectious disease, mitigation of threats posed by irresponsible or nefarious use of biological technologies, and enhanced development of new resources derived from synthetic biology, such as novel chemicals, materials, and coatings with useful, unique properties.

Achieving such ambitious goals, however, will require more complete knowledge about how gene editors, and derivative technologies including gene drives, function at various physical and temporal scales under different environmental conditions, across multiple generations of an organism. In parallel, demonstrating the ability to precisely control gene edits, turning them on and off under certain conditions or even reversing their effects entirely, will be paramount to translation of these tools to practical applications…

Each of the seven teams will pursue one or more of three technical objectives: develop genetic constructs—biomolecular “instructions”—that provide spatial, temporal, and reversible control of genome editors in living systems; devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states. Safe Genes research will not involve any releases of organisms into the environment; however, the research—performed in contained facilities—could inform potential future applications, including safe, predictable, and reversible gene drives….

A Harvard Medical School team led by Dr. George Church seeks to develop systems to safeguard genomes by detecting, preventing, and ultimately reversing mutations that may arise from exposure to radiation. This work will involve creation of novel computational and molecular tools to enable the development of precise editors that can distinguish between highly similar genetic sequences. The team also plans to screen the effectiveness of natural and synthetic drugs to inhibit gene editing activity.

A North Carolina State University (NCSU) team led by Dr. John Godwin aims to develop and test a mammalian gene drive system in rodents. The team’s genetic technique targets population-specific genetic variants found only in particular invasive communities of animals. If successful, the work will expand the tools available to manage invasive species that threaten biodiversity and human food security, and that serve as potential reservoirs of infectious diseases affecting native animal and human populations….

A University of California, Berkeley team led by Dr. Jennifer Doudna will investigate the development of novel, safe gene editing tools for use as antiviral agents in animal models, targeting the Zika and Ebola viruses. The team will also aim to identify anti-CRISPR proteins capable of inhibiting unwanted genome-editing activity, while developing novel strategies for delivery of genome editors and inhibitors….

A University of California, Riverside team led by Dr. Omar Akbari seeks to develop robust and reversible gene drive systems for control of Aedes aegypti mosquito populations.

Excerpts from Building the Safe Genes Toolkit, DARPA Press Release, July 19, 2017

Pandemic Counter-Measures: DARPA

The US military supports US Government responses to public health emergencies such as Ebola, which can cause regional destabilization and spread through global travel. Warfighters must also operate in regions where diseases like chikungunya and dengue are endemic, and even seemingly mild challenges like seasonal influenza affect force readiness. In addition to these naturally occurring threats, terrorists and other potential adversaries have a growing palette of biological tools to engineer new biological threats. Existing capabilities to respond to an outbreak and develop therapeutics often take years or even decades to achieve results. Recent examples of public health emergencies have demonstrated a national and global inability to develop effective preventive or therapeutic solutions in a relevant timescale when an infectious threat emerges. The threat of infectious agents on US and global national security can be mitigated if the DoD has the capability to rapidly deploy and impart near-immediate immunity to military personnel and civilian populations for known and newly emerging pathogens.

The goal of P3 is to achieve an integrated capability that can deliver pandemic prevention countermeasures to patients within 60 days of an outbreak. P3 aims to revolutionize outbreak response by enabling rapid discovery, characterization, production, and testing of efficacious medical countermeasures. P3 will innovate in the following areas: (1) Generation of virus stock (including viral unknowns); (2) Rapid evolution of antibody candidates; and (3) Gene-encoded antibody delivery methods.

Excerpts from  The Biological Technologies Office (BTO) of the Defense Advanced Research Projects Agency (DARPA) Proposers Day March 2, 2017 

Bio-Materials: DARPA

Consider the benefits to be gained from a chimney that heals after damage, a roof that breathes to control airflow, surfaces that don’t flake or fade, and a driveway that eats oil to clean up after spills.–From the DARPA website

The structural materials that are currently used to construct homes, buildings, and infrastructure are expensive to produce and transport, wear out due to age and damage, and have limited ability to respond to changes in their immediate surroundings. Living biological materials—bone, skin, bark, and coral, for example—have attributes that provide advantages over the non-living materials people build with, in that they can be grown where needed, self-repair when damaged, and respond to changes in their surroundings. The inclusion of living materials in human-built environments could offer significant benefits; however, today scientists and engineers are unable to easily control the size and shape of living materials in ways that would make them useful for construction.

DARPA is launching the Engineered Living Materials (ELM) program with a goal of creating a new class of materials that combines the structural properties of traditional building materials with attributes of living systems. Living materials represent a new opportunity to leverage engineered biology to solve existing problems associated with the construction and maintenance of built environments, and to create new capabilities to craft smart infrastructure that dynamically responds to its surroundings.

“The vision of the ELM program is to grow materials on demand where they are needed,” said ELM program manager Justin Gallivan. “Imagine that instead of shipping finished materials, we can ship precursors and rapidly grow them on site using local resources. And, since the materials will be alive, they will be able to respond to changes in their environment and heal themselves in response to damage.”…

Scientists are making progress with three-dimensional printing of living tissues and organs, using scaffolding materials that sustain the long-term viability of the living cells. These cells are derived from existing natural tissues, however, and are not engineered to perform synthetic functions. And current cell-printing methods are too expensive to produce building materials at necessary scales.

ELM looks to merge the best features of these existing technologies and build on them to create hybrid materials composed of non-living scaffolds that give structure to and support the long-term viability of engineered living cells. DARPA intends to develop platform technologies that are scalable and generalizable to facilitate a quick transition from laboratory to commercial applications.

The long-term objective of the ELM program is to develop an ability to engineer structural properties directly into the genomes of biological systems so that neither scaffolds nor external development cues are needed for an organism to realize the desired shape and properties. ….

Work on ELM will be fundamental research carried out in controlled laboratory settings. DARPA does not anticipate environmental release during the program.

Excerpts from Living Structural Materials  Could Open New Horizons for Engineers and Architects, DARPA seeks to develop design tools and methods for creating programmable, self-healing, living building materials, OUTREACH@DARPA.MIL, Aug. 5, 2016

See also FBO.org

Animal Diseases as Biological Weapons

The World Health Organisation (WHO), animal health and national defence officers called for wider international co-operation to avoid the spread of animal diseases that could be used as biological weapons.  Sixty percent of human diseases come from animal agents and 80% of the agents that could be used for bio-terrorism are of animal origin, said Bernard Vallat, director general of the World Organisation for Animal Health (OIE).

“History has shown animal diseases have often been used as weapons before. Advances in genetics can now make them even more harmful. So we are calling for further investment to be made at national level on bio-security,” Vallat said at a conference on biological threat reduction.  Diseases have spread from animals to humans for millennia, with latest examples including the bird flu virus that has killed hundreds of people around the globe.

The OIE and the WHO warned animal disease agents could escape naturally, accidentally but also intentionally from laboratories, to be used as bio-weapons….Security breaches involving animal diseases are not rare.  The Pentagon said in May 2015 and June the US military had sent live samples of anthrax, which can be used as biological weapon, to five countries outside the United States and to dozens of US labs.

Excerpts from Beware of animal diseases as biological weapons, health experts say, Reuters, June 30, 2015

How to Engineer Mars to Become Earth

Modifying a planet’s atmosphere to make it habitable for humans could be a possibility, according to the Pentagon’s Defense Advanced Research Projects Agency.  Darpa has announced it is developing terraforming technology in a bid to recreate the conditions needed for live to thrive….[DARPA is developing]…  a ‘technological toolkit’ to transform hostile places. It will involve genetically engineering a wide variety of organisms.   Alicia Jackson, the deputy director of Darpa’s Biological Technologies Office in Virginia, made comments alluding to the technology at a biotech conference on June 22, 2015

‘For the first time, we have the technological toolkit to transform not just hostile places here on Earth, but to go into space not just to visit, but to stay,’ she was quoted as saying…This ‘toolkit’ will involve genetically engineering organisms of all types, of which there are up to 30 billion on Earth. On Earth, most synthetic biology projects use just two at the moment – e. coli and yeast. A newly developed software called DTA GView, dubbed the ‘Google Maps of genomes,’ will help scientists correlate information on organisms.  And the ultimate goal is to choose organisms with specific genes to create something with certain characteristics.

For example, it has been theorised that some organisms could be bio-engineered to pull certain gases out of the Martian atmosphere – like carbon dioxide – and create nitrogen and oxygen.  Both are abundant in Earth’s atmosphere – and would be needed for any humans hoping to breathe on Mars without a spacesuit.  NASA has toyed with the idea before; last year, they unveiled the Mars Ecopoiesis Test Bed concept, which would create ecosystems capable of supporting life within biodomes on Mars.   But Darpa’s technology would creative liveable environments outside in the open air on the Martian surface.

The technology has other uses, too; it could be used to repair an environment on Earth after a manmade or natural disaster, although Darpa did not specify what these could be.

Excerpts from: JONATHAN O’CALLAGHAN Could we turn Mars into Earth 2.0? Darpa is working on designer organisms to terraform the red planet, Daily Mail, June 26, 2015