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A transatlantic report highlighting the risks and opportunities associated with synthetic biology and bioengineering

I love e-Life, the open access journal where its editors noted that a submitted synthetic biology and bioengineering report was replete with US and UK experts (along with a European or two) but no expert input from other parts of the world. In response the authors added ‘transatlantic’ to the title. It was a good decision since it was too late to add any new experts if the authors planned to have their paper published in the foreseeable future.

I’ve commented many times here when panels of experts include only Canadian, US, UK, and, sometimes, European or Commonwealth (Australia/New Zealand) experts that we need to broaden our perspectives and now I can add: or at least acknowledge (e.g. transatlantic) that the perspectives taken are reflective of a rather narrow range of countries.

Now getting to the report, here’s more from a November 21, 2017 University of Cambridge press release,

Human genome editing, 3D-printed replacement organs and artificial photosynthesis – the field of bioengineering offers great promise for tackling the major challenges that face our society. But as a new article out today highlights, these developments provide both opportunities and risks in the short and long term.

Rapid developments in the field of synthetic biology and its associated tools and methods, including more widely available gene editing techniques, have substantially increased our capabilities for bioengineering – the application of principles and techniques from engineering to biological systems, often with the goal of addressing ‘real-world’ problems.

In a feature article published in the open access journal eLife, an international team of experts led by Dr Bonnie Wintle and Dr Christian R. Boehm from the Centre for the Study of Existential Risk at the University of Cambridge, capture perspectives of industry, innovators, scholars, and the security community in the UK and US on what they view as the major emerging issues in the field.

Dr Wintle says: “The growth of the bio-based economy offers the promise of addressing global environmental and societal challenges, but as our paper shows, it can also present new kinds of challenges and risks. The sector needs to proceed with caution to ensure we can reap the benefits safely and securely.”

The report is intended as a summary and launching point for policy makers across a range of sectors to further explore those issues that may be relevant to them.

Among the issues highlighted by the report as being most relevant over the next five years are:

Artificial photosynthesis and carbon capture for producing biofuels

If technical hurdles can be overcome, such developments might contribute to the future adoption of carbon capture systems, and provide sustainable sources of commodity chemicals and fuel.

Enhanced photosynthesis for agricultural productivity

Synthetic biology may hold the key to increasing yields on currently farmed land – and hence helping address food security – by enhancing photosynthesis and reducing pre-harvest losses, as well as reducing post-harvest and post-consumer waste.

Synthetic gene drives

Gene drives promote the inheritance of preferred genetic traits throughout a species, for example to prevent malaria-transmitting mosquitoes from breeding. However, this technology raises questions about whether it may alter ecosystems [emphasis mine], potentially even creating niches where a new disease-carrying species or new disease organism may take hold.

Human genome editing

Genome engineering technologies such as CRISPR/Cas9 offer the possibility to improve human lifespans and health. However, their implementation poses major ethical dilemmas. It is feasible that individuals or states with the financial and technological means may elect to provide strategic advantages to future generations.

Defence agency research in biological engineering

The areas of synthetic biology in which some defence agencies invest raise the risk of ‘dual-use’. For example, one programme intends to use insects to disseminate engineered plant viruses that confer traits to the target plants they feed on, with the aim of protecting crops from potential plant pathogens – but such technologies could plausibly also be used by others to harm targets.

In the next five to ten years, the authors identified areas of interest including:

Regenerative medicine: 3D printing body parts and tissue engineering

While this technology will undoubtedly ease suffering caused by traumatic injuries and a myriad of illnesses, reversing the decay associated with age is still fraught with ethical, social and economic concerns. Healthcare systems would rapidly become overburdened by the cost of replenishing body parts of citizens as they age and could lead new socioeconomic classes, as only those who can pay for such care themselves can extend their healthy years.

Microbiome-based therapies

The human microbiome is implicated in a large number of human disorders, from Parkinson’s to colon cancer, as well as metabolic conditions such as obesity and type 2 diabetes. Synthetic biology approaches could greatly accelerate the development of more effective microbiota-based therapeutics. However, there is a risk that DNA from genetically engineered microbes may spread to other microbiota in the human microbiome or into the wider environment.

Intersection of information security and bio-automation

Advancements in automation technology combined with faster and more reliable engineering techniques have resulted in the emergence of robotic ‘cloud labs’ where digital information is transformed into DNA then expressed in some target organisms. This opens the possibility of new kinds of information security threats, which could include tampering with digital DNA sequences leading to the production of harmful organisms, and sabotaging vaccine and drug production through attacks on critical DNA sequence databases or equipment.

Over the longer term, issues identified include:

New makers disrupt pharmaceutical markets

Community bio-labs and entrepreneurial startups are customizing and sharing methods and tools for biological experiments and engineering. Combined with open business models and open source technologies, this could herald opportunities for manufacturing therapies tailored to regional diseases that multinational pharmaceutical companies might not find profitable. But this raises concerns around the potential disruption of existing manufacturing markets and raw material supply chains as well as fears about inadequate regulation, less rigorous product quality control and misuse.

Platform technologies to address emerging disease pandemics

Emerging infectious diseases—such as recent Ebola and Zika virus disease outbreaks—and potential biological weapons attacks require scalable, flexible diagnosis and treatment. New technologies could enable the rapid identification and development of vaccine candidates, and plant-based antibody production systems.

Shifting ownership models in biotechnology

The rise of off-patent, generic tools and the lowering of technical barriers for engineering biology has the potential to help those in low-resource settings, benefit from developing a sustainable bioeconomy based on local needs and priorities, particularly where new advances are made open for others to build on.

Dr Jenny Molloy comments: “One theme that emerged repeatedly was that of inequality of access to the technology and its benefits. The rise of open source, off-patent tools could enable widespread sharing of knowledge within the biological engineering field and increase access to benefits for those in developing countries.”

Professor Johnathan Napier from Rothamsted Research adds: “The challenges embodied in the Sustainable Development Goals will require all manner of ideas and innovations to deliver significant outcomes. In agriculture, we are on the cusp of new paradigms for how and what we grow, and where. Demonstrating the fairness and usefulness of such approaches is crucial to ensure public acceptance and also to delivering impact in a meaningful way.”

Dr Christian R. Boehm concludes: “As these technologies emerge and develop, we must ensure public trust and acceptance. People may be willing to accept some of the benefits, such as the shift in ownership away from big business and towards more open science, and the ability to address problems that disproportionately affect the developing world, such as food security and disease. But proceeding without the appropriate safety precautions and societal consensus—whatever the public health benefits—could damage the field for many years to come.”

The research was made possible by the Centre for the Study of Existential Risk, the Synthetic Biology Strategic Research Initiative (both at the University of Cambridge), and the Future of Humanity Institute (University of Oxford). It was based on a workshop co-funded by the Templeton World Charity Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation programme.

Here’s a link to and a citation for the paper,

A transatlantic perspective on 20 emerging issues in biological engineering by Bonnie C Wintle, Christian R Boehm, Catherine Rhodes, Jennifer C Molloy, Piers Millett, Laura Adam, Rainer Breitling, Rob Carlson, Rocco Casagrande, Malcolm Dando, Robert Doubleday, Eric Drexler, Brett Edwards, Tom Ellis, Nicholas G Evans, Richard Hammond, Jim Haseloff, Linda Kahl, Todd Kuiken, Benjamin R Lichman, Colette A Matthewman, Johnathan A Napier, Seán S ÓhÉigeartaigh, Nicola J Patron, Edward Perello, Philip Shapira, Joyce Tait, Eriko Takano, William J Sutherland. eLife; 14 Nov 2017; DOI: 10.7554/eLife.30247

This paper is open access and the editors have included their notes to the authors and the authors’ response.

You may have noticed that I highlighted a portion of the text concerning synthetic gene drives. Coincidentally I ran across a November 16, 2017 article by Ed Yong for The Atlantic where the topic is discussed within the context of a project in New Zealand, ‘Predator Free 2050’ (Note: A link has been removed),

Until the 13th century, the only land mammals in New Zealand were bats. In this furless world, local birds evolved a docile temperament. Many of them, like the iconic kiwi and the giant kakapo parrot, lost their powers of flight. Gentle and grounded, they were easy prey for the rats, dogs, cats, stoats, weasels, and possums that were later introduced by humans. Between them, these predators devour more than 26 million chicks and eggs every year. They have already driven a quarter of the nation’s unique birds to extinction.

Many species now persist only in offshore islands where rats and their ilk have been successfully eradicated, or in small mainland sites like Zealandia where they are encircled by predator-proof fences. The songs in those sanctuaries are echoes of the New Zealand that was.

But perhaps, they also represent the New Zealand that could be.

In recent years, many of the country’s conservationists and residents have rallied behind Predator-Free 2050, an extraordinarily ambitious plan to save the country’s birds by eradicating its invasive predators. Native birds of prey will be unharmed, but Predator-Free 2050’s research strategy, which is released today, spells doom for rats, possums, and stoats (a large weasel). They are to die, every last one of them. No country, anywhere in the world, has managed such a task in an area that big. The largest island ever cleared of rats, Australia’s Macquarie Island, is just 50 square miles in size. New Zealand is 2,000 times bigger. But, the country has committed to fulfilling its ecological moonshot within three decades.

In 2014, Kevin Esvelt, a biologist at MIT, drew a Venn diagram that troubles him to this day. In it, he and his colleagues laid out several possible uses for gene drives—a nascent technology for spreading designer genes through groups of wild animals. Typically, a given gene has a 50-50 chance of being passed to the next generation. But gene drives turn that coin toss into a guarantee, allowing traits to zoom through populations in just a few generations. There are a few natural examples, but with CRISPR, scientists can deliberately engineer such drives.

Suppose you have a population of rats, roughly half of which are brown, and the other half white. Now, imagine there is a gene that affects each rat’s color. It comes in two forms, one leading to brown fur, and the other leading to white fur. A male with two brown copies mates with a female with two white copies, and all their offspring inherit one of each. Those offspring breed themselves, and the brown and white genes continue cascading through the generations in a 50-50 split. This is the usual story of inheritance. But you can subvert it with CRISPR, by programming the brown gene to cut its counterpart and replace it with another copy of itself. Now, the rats’ children are all brown-furred, as are their grandchildren, and soon the whole population is brown.

Forget fur. The same technique could spread an antimalarial gene through a mosquito population, or drought-resistance through crop plants. The applications are vast, but so are the risks. In theory, gene drives spread so quickly and relentlessly that they could rewrite an entire wild population, and once released, they would be hard to contain. If the concept of modifying the genes of organisms is already distasteful to some, gene drives magnify that distaste across national, continental, and perhaps even global scales.

These excerpts don’t do justice to this thought-provoking article. If you have time, I recommend reading it in its entirety  as it provides some insight into gene drives and, with some imagination on the reader’s part, the potential for the other technologies discussed in the report.

One last comment, I notice that Eric Drexler is cited as on the report’s authors. He’s familiar to me as K. Eric Drexler, the author of the book that popularized nanotechnology in the US and other countries, Engines of Creation (1986) .

Does understanding your pet mean understanding artificial intelligence better?

Heather Roff’s take on artificial intelligence features an approach I haven’t seen before. From her March 30, 2017 essay for The Conversation (h/t March 31, 2017 news item on phys.org),

It turns out, though, that we already have a concept we can use when we think about AI: It’s how we think about animals. As a former animal trainer (albeit briefly) who now studies how people use AI, I know that animals and animal training can teach us quite a lot about how we ought to think about, approach and interact with artificial intelligence, both now and in the future.

Using animal analogies can help regular people understand many of the complex aspects of artificial intelligence. It can also help us think about how best to teach these systems new skills and, perhaps most importantly, how we can properly conceive of their limitations, even as we celebrate AI’s new possibilities.
Looking at constraints

As AI expert Maggie Boden explains, “Artificial intelligence seeks to make computers do the sorts of things that minds can do.” AI researchers are working on teaching computers to reason, perceive, plan, move and make associations. AI can see patterns in large data sets, predict the likelihood of an event occurring, plan a route, manage a person’s meeting schedule and even play war-game scenarios.

Many of these capabilities are, in themselves, unsurprising: Of course a robot can roll around a space and not collide with anything. But somehow AI seems more magical when the computer starts to put these skills together to accomplish tasks.

Thinking of AI as a trainable animal isn’t just useful for explaining it to the general public. It is also helpful for the researchers and engineers building the technology. If an AI scholar is trying to teach a system a new skill, thinking of the process from the perspective of an animal trainer could help identify potential problems or complications.

For instance, if I try to train my dog to sit, and every time I say “sit” the buzzer to the oven goes off, then my dog will begin to associate sitting not only with my command, but also with the sound of the oven’s buzzer. In essence, the buzzer becomes another signal telling the dog to sit, which is called an “accidental reinforcement.” If we look for accidental reinforcements or signals in AI systems that are not working properly, then we’ll know better not only what’s going wrong, but also what specific retraining will be most effective.

This requires us to understand what messages we are giving during AI training, as well as what the AI might be observing in the surrounding environment. The oven buzzer is a simple example; in the real world it will be far more complicated.

Before we welcome our AI overlords and hand over our lives and jobs to robots, we ought to pause and think about the kind of intelligences we are creating. …

Source: pixabay.com

It’s just last year (2016) that an AI system beat a human Go master player. Here’s how a March 17, 2016 article by John Russell for TechCrunch described the feat (Note: Links have been removed),

Much was written of an historic moment for artificial intelligence last week when a Google-developed AI beat one of the planet’s most sophisticated players of Go, an East Asia strategy game renowned for its deep thinking and strategy.

Go is viewed as one of the ultimate tests for an AI given the sheer possibilities on hand. “There are 1,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000 possible positions [in the game] — that’s more than the number of atoms in the universe, and more than a googol times larger than chess,” Google said earlier this year.

If you missed the series — which AlphaGo, the AI, won 4-1 — or were unsure of exactly why it was so significant, Google summed the general importance up in a post this week.

Far from just being a game, Demis Hassabis, CEO and Co-Founder of DeepMind — the Google-owned company behind AlphaGo — said the AI’s development is proof that it can be used to solve problems in ways that humans may be not be accustomed or able to do:

We’ve learned two important things from this experience. First, this test bodes well for AI’s potential in solving other problems. AlphaGo has the ability to look “globally” across a board—and find solutions that humans either have been trained not to play or would not consider. This has huge potential for using AlphaGo-like technology to find solutions that humans don’t necessarily see in other areas.

I find Roff’s thesis intriguing and is likely applicable to the short-term but in the longer term and in light of the attempts to  create devices that mimic neural plasticity and neuromorphic engineering  I don’t find her thesis convincing.

Fido’s osteosarcoma and nanoparticle drug delivery

Researchers at the University of Illinois at Urbana-Champaign have started testing nanoparticle drug delivery for bone tumours in dogs. From a July 25, 2016 news item on ScienceDaily,

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs — mammals closer in size and biology to humans — with naturally occurring bone cancers, which also are a lot like human bone tumors.

A July 25, 2016 University of Illinois at Urbana-Champaign news release (also on EurekAlert) by Diana Yates, which originated the news item, provides more detail about the research,

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I. veterinary clinical medicine professor Dr. Timothy Fan, who led the study with materials science and engineering professor Jianjun Cheng. All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.” Fan is a faculty member of the Anticancer Discovery from Pets to People research theme at the IGB [Institute for Genomic Biology).

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng, an affiliate of the IGB’s Regenerative Biology & Tissue Engineering theme, said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

Here’s a link to and a citation for the paper,

Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis by Qian Yin, Li Tang, Kaimin Cai, Rong Tong, Rachel Sternberg, Xujuan Yang, Lawrence W. Dobrucki, Luke B. Borst, Debra Kamstock, Ziyuan Song, William G. Helferich, Jianjun Cheng, and Timothy M. Fan. Proceedings of the National Academy of Sciences 2016 doi: 10.1073/pnas.1603316113

This paper is behind a paywall.

Animal technology: a touchscreen for your dog, sonar lunch orders for dolphins, and more

A rather unexpected (for ignorant folks like me) approach to animal technology has been taken by Ilyena Hirskyj-Douglas in her June 17, 2016 piece on phys.org,

Imagine leaving your dog at home while it turns on the smart TV and chooses a programme to watch. Meanwhile you visit a zoo where you play interactive touchscreen games with the apes and watch the dolphins using sonar to order their lunch. In the field behind you, a farmer is stroking his flock of chickens virtually, leaving the drones to collect sheep while the cows milk themselves. Welcome to the unusual world of animal technology.

Hirskyj-Douglas’s piece was originally published as a June 15, 2016 essay  about animal-computer interaction (ACI) and some of the latest work being done in the field on The Conversation website (Note: Links have been removed),

Animals have interacted with technology for a long time, from tracking devices for conservation research to zoos with early touchscreen computers. But more recently, the field of animal-computer interaction (ACI) has begun to explore in more detail exactly how animals use technology like this. The hope is that better understanding animals’ relationship with technology will means we can use it to monitor and improve their welfare.

My own research involves building intelligent tracking devices for dogs that let them interact with media on a screen so we can study how dogs use TV and what they like to watch (if anything). Perhaps unsurprisingly, I’ve found that dogs like to watch videos of other dogs. This has led me to track dogs dogs’ gaze across individual and multiple screens and attempts to work out how best to make media just for dogs.

Eventually I hope to make an interactive system that allows a dog to pick what they want to watch and that evolves by learning what media they like. This isn’t to create a toy for indulgent pet owners. Dogs are often left at home alone during the day or isolated in kennels. So interactive media technology could improve the animals’ welfare by providing a stimulus and a source of entertainment. …

This 2014 video (embedded in Hirskyj-Douglas’s essay) illustrates how touchscreens are used by great apes,

It’s all quite intriguing and I encourage you to read the essay in it entirety.

If you find the great apes project interesting, you can find  out more about it (I believe it’s in the Primate Research category) and others at the Atlanta Zoo’s research webpage.

A dog’s intimate understanding of chemical communication: sniffing butts

The American Chemical Society (ACS) has made available a video which answers a question almost everyone has asked at one time or another, why do dogs sniff each other’s bottoms?

Here’s how a July 28, 2014 ACS news release describes this line of inquiry,

Here at Reactions, we ask the tough questions to get to the bottom of the biggest scientific quandaries. In that spirit, this week’s video explains why dogs sniff each other’s butts. It’s a somewhat silly question with a surprisingly complex answer. This behavior is just one of many interesting forms of chemical communication in the animal kingdom

Without more ado, the video,

You can find more videos in ACS’s Reactions series here. (This series was formerly known as Bitesize Science.)