Category Archives: synthetic biology

Teaching molecular and synthetic biology in grades K-12

This* story actually started in 2018 with an August 1, 2018 Harvard University news release (h/t Aug. 1, 2018 news item on phys.org) by Leslie Brownell announcing molecular and synthetic biology educational kits that been tested in the classroom. (In 2019, a new kit was released but more about that later.)

As biologists have probed deeper into the molecular and genetic underpinnings of life, K-12 schools have struggled to provide a curriculum that reflects those advances. Hands-on learning is known to be more engaging and effective for teaching science to students, but even the most basic molecular and synthetic biology experiments require equipment far beyond an average classroom’s budget, and often involve the use of bacteria and other substances that can be difficult to manage outside a controlled lab setting.

Now, a collaboration between the Wyss Institute at Harvard University, MIT [Massachusetts Institute of Technology], and Northwestern University has developed BioBits, new educational biology kits that use freeze-dried cell-free (FD-CF) reactions to enable students to perform a range of simple, hands-on biological experiments. The BioBits kits introduce molecular and synthetic biology concepts without the need for specialized lab equipment, at a fraction of the cost of current standard experimental designs. The kits are described in two papers published in Science Advances [2018].

“The main motivation in developing these kits was to give students fun activities that allow them to actually see, smell, and touch the outcomes of the biological reactions they’re doing at the molecular level,” said Ally Huang, a co-first author on both papers who is an MIT graduate student in the lab of Wyss Founding Core Faculty member Jim Collins, Ph.D. “My hope is that they will inspire more kids to consider a career in STEM [science, technology, engineering, and math] and, more generally, give all students a basic understanding of how biology works, because they may one day have to make personal or policy decisions based on modern science.”

Synthetic and molecular biology frequently make use of the cellular machinery found in E. coli bacteria to produce a desired protein. But this system requires that the bacteria be kept alive and contained for an extended period of time, and involves several complicated preparation and processing steps. The FD-CF reactions pioneered in Collins’ lab for molecular manufacturing, when combined with innovations from the lab of Michael Jewett, Ph.D. at Northwestern University, offer a solution to this problem by removing bacteria from the equation altogether.

“You can think of it like opening the hood of a car and taking the engine out: we’ve taken the ‘engine’ that drives protein production out of a bacterial cell and given it the fuel it needs, including ribosomes and amino acids, to create proteins from DNA outside of the bacteria itself,” explained Jewett, who is the Charles Deering McCormick Professor of Teaching Excellence at Northwestern University’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology, and co-corresponding author of both papers. This collection of molecular machinery is then freeze-dried into pellets so that it becomes shelf-stable at room temperature. To initiate the transcription of DNA into RNA and the translation of that RNA into a protein, a student just needs to add the desired DNA and water to the freeze-dried pellets.

The researchers designed a range of molecular experiments that can be performed using this system, and coupled each of them to a signal that the students can easily detect with their sense of sight, smell, or touch. The first, called BioBits Bright, contains six different freeze-dried DNA templates that each encode a protein that fluoresces a different color when illuminated with blue light. To produce the proteins, students simply add these DNA templates and water to the FD-CF machinery and put the reactions in an inexpensive incubator (~$30) for several hours, and then view them with a blue light illuminator (~$15). The students can also design their own experiments to produce a desired collection of colors that they can then arrange into a visual image, a bit like using a Light Brite ©. “Challenging the students to build their own in vitro synthetic programs also allows educators to start to talk about how synthetic biologists might control biology to make important products, such as medicines or chemicals,” explained Jessica Stark, an NSF Graduate Research Fellow in the Jewett lab at Northwestern University who is co-first author on both papers.

An expansion of the BioBits Bright kit, called BioBits Explorer, includes experiments that engage the senses of smell and touch and allow students to probe their environment using designer synthetic biosensors. In the first experiment, the FD-CF reaction pellets contain a gene that drives the conversion of isoamyl alcohol to isoamyl acetate, a compound that produces a strong banana odor. In the second experiment, the FD-CF reactions contain a gene coding for the enzyme sortase, which recognizes and links specific segments of proteins in a liquid solution together to form a squishy, semi-solid hydrogel, which the students can touch and manipulate. The third module uses another Wyss technology, the toehold switch sensor, to identify DNA extracted from a banana or a kiwi. The sensors are hairpin-shaped RNA molecules designed such that when they bind to a “trigger” RNA, they spring open and reveal a genetic sequence that produces a fluorescent protein. When fruit DNA is added to the sensor-containing FD-CF pellets, only the sensors that are designed to open in the presence of each fruit’s RNA will produce the fluorescent protein.

The researchers tested their BioBits kits in the Chicago Public School system, and demonstrated that students and teachers were able to perform the experiments in the kits with the same success as trained synthetic biology researchers. In addition to refining the kits’ design so that they can one day provide them to classrooms around the world, the authors hope to create an open-source online database where teachers and students can share their results and ideas for ways to modify the kits to explore different biological questions.

“Synthetic biology is going to be one of the defining technologies of the century, and yet it has been challenging to teach the fundamental concepts of the field in K-12 classrooms given that such efforts often require expensive, complicated equipment,” said Collins, who is a co-corresponding author of both papers and also the Termeer Professor of Medical Engineering & Science at MIT. “We show that it is possible to use freeze-dried, cell-free extracts along with freeze-dried synthetic biology components to conduct innovative educational experiments in classrooms and other low-resource settings. The BioBits kits enable us to expose young kids, older kids, and even adults to the wonders of synthetic biology and, as a result, are poised to transform science education and society.

“All scientists are passionate about what they do, and we are frustrated by the difficulty our educational system has had in inciting a similar level of passion in young people. This BioBits project demonstrates the kind of out-of-the-box thinking and refusal to accept the status quo that we value and cultivate at the Wyss Institute, and we all hope it will stimulate young people to be intrigued by science,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s exciting to see this project move forward and become available to biology classrooms worldwide and, hopefully some of these students will pursue a path in science because of their experience.”

Additional authors of the papers include Peter Nguyen, Ph.D., Nina Donghia, and Tom Ferrante from the Wyss Institute; Melissa Takahashi, Ph.D. and Aaron Dy from MIT; Karen Hsu and Rachel Dubner from Northwestern University; Keith Pardee, Ph.D., Assistant Professor at the University of Toronto; and a number of teachers and students in the Chicago school system including: Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Tom Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander Hill, Jemima Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzales, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, and TaRhonda Woods.

This research was supported by the Army Research Office, the National Science Foundation, the Air Force Research Laboratory Center of Excellence Grant, The Defense Threat Reduction Agency Grant, the David and Lucile Packard Foundation, the Camille Dreyfus Teacher-Scholar Program, the Wyss Institute at Harvard University, the Paul G. Allen Frontiers Group, The Air Force Office of Scientific Research, and the Natural Sciences and Engineering Council of Canada. [emphases mine]

Well, that list of funding agencies is quite interesting. The US Army and Air Force but not the Navy? As for what the Natural Sciences and Engineering Council of Canada is doing on that list, I can only imagine why.

This is what they were doing in 2018,

Now for the latest update, a May 7, 2019 news item on phys.org announces the BioBits Kits have been expanded,

How can high school students learn about a technology as complex and abstract as CRISPR? It’s simple: just add water.

A Northwestern University-led team has developed BioBits, a suite of hands-on educational kits that enable students to perform a range of biological experiments by adding water and simple reagents to freeze-dried cell-free reactions. The kits link complex biological concepts to visual, fluorescent readouts, so students know—after a few hours and with a single glance—the results of their experiments.

A May 7, 2019 Northwestern University news release (also on EurekAlert and received via email) by Amanda Morris, which originated the news item, provides more details,

After launching BioBits last summer, the researchers are now expanding the kit to include modules for CRISPR [clustered regularly interspaced short palindromic repeats] and antibiotic resistance. A small group of Chicago-area teachers and high school students just completed the first pilot study for these new modules, which include interactive experiments and supplementary materials exploring ethics and strategies.

“After we unveiled the first kits, we next wanted to tackle current topics that are important for society,” said Northwestern’s Michael Jewett, principal investigator of the study. “That led us to two areas: antibiotic resistance and gene editing.”

Called BioBits Health, the new kits and pilot study are detailed in a paper published today (May 7 [2019]) in the journal ACS Synthetic Biology.

Jewett is a professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology. Jessica Stark, a graduate student in Jewett’s laboratory, led the study.

Test in a tube

Instead of using live cells, the BioBits team removed the essential cellular machinery from inside the cells and freeze-dried them for shelf stability. Keeping cells alive and contained for an extended period of time involves several complicated, time-consuming preparation and processing steps as well as expensive equipment. Freeze-dried cell-free reactions bypass those complications and costs.

“These are essentially test-tube biological reactions,” said Stark, a National Science Foundation graduate research fellow. “We break the cells open and use their guts, which still contain all of the necessary biological machinery to carry out a reaction. We no longer need living cells to demonstrate biology.”

This method to harness biological systems without intact, living cells became possible over the last two decades thanks to multiple innovations, including many in cell-free synthetic biology by Jewett’s lab. Not only are these experiments doable in the classroom, they also only cost pennies compared to standard high-tech experimental designs.

“I’m hopeful that students get excited about engineering biology and want to learn more,” Jewett said.

Conquering CRISPR

One of the biggest scientific breakthroughs of the past decade, CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats. The powerful gene-editing technology uses enzymes to cut DNA in precise locations to turn off or edit targeted genes. It could be used to halt genetic diseases, develop new medicines, make food more nutritious and much more.

BioBits Health uses three components required for CRISPR: an enzyme called the Cas9 protein, a target DNA sequence encoding a fluorescent protein and an RNA molecule that targets the fluorescent protein gene. When students add all three components — and water — to the freeze-dried cell-free system, it creates a reaction that edits, or cuts, the DNA for the fluorescent protein. If the DNA is cut, the system does not glow. If the DNA is not cut, the fluorescent protein is made, and the system glows fluorescent.

“We have linked this abstract, really advanced biological concept to the presence or absence of a fluorescent protein,” Stark said. “It’s something students can see, something they can visually understand.”

The curriculum also includes activities that challenge students to consider the ethical questions and dilemmas surrounding the use of gene-editing technologies.

“There is a lot of excitement about being able to edit genomes with these technologies,” Jewett said. “BioBits Health calls attention to a lot of important questions — not only about how CRISPR technology works but about ethics that society should be thinking about. We hope that this promotes a conversation and dialogue about such technologies.”

Reducing resistance

Jewett and Stark are both troubled by a prediction that, by the year 2050, drug-resistant bacterial infections could outpace cancer as a leading cause of death. This motivated them to help educate the future generation of scientists about how antibiotic resistance emerges and inspire them to take actions that could help limit the emergence of resistant bacteria.
In this module, students run two sets of reactions to produce a glowing fluorescent protein — one set with an antibiotic resistance gene and one set without. Students then add antibiotics. If the experiment glows, the fluorescent protein has been made, and the reaction has become resistant to antibiotics. If the experiment does not glow, then the antibiotic has worked.

“Because we’re using cell-free systems rather than organisms, we can demonstrate drug resistance in a way that doesn’t create drug-resistant bacteria,” Stark explained. “We can demonstrate these concepts without the risks.”

A supporting curriculum piece challenges students to brainstorm and research strategies for slowing the rate of emerging antibiotic resistant strains.

Part of something cool

After BioBits was launched in summer 2018, 330 schools from around the globe requested prototype kits for their science labs. The research team, which includes members from Northwestern and MIT, has received encouraging feedback from teachers, students and parents.

“The students felt like scientists and doctors by touching and using the laboratory materials provided during the demo,” one teacher said. “Even the students who didn’t seem engaged were secretly paying attention and wanted to take their turn pipetting. They knew they were part of something really cool, so we were able to connect with them in a way that was new to them.”

“My favorite part was using the equipment,” a student said. “It was a fun activity that immerses you into what top scientists are currently doing.”

###

The study, “BioBits Health: Classroom activities exploring engineering, biology and human health with fluorescent readouts,” was supported by the Army Research Office (award number W911NF-16-1-0372), the National Science Foundation (grant numbers MCB-1413563 and MCB-1716766), the Air Force Research Laboratory Center of Excellence (grant number FA8650-15-2-5518), the Defense Threat Reduction Agency (grant number HDTRA1-15-10052/P00001), the Department of Energy (grant number DE-SC0018249), the Human Frontiers Science Program (grant number RGP0015/2017), the David and Lucile Packard Foundation, the Office of Energy Efficiency and Renewable Energy (grant number DE-EE008343) and the Camille Dreyfus Teacher-Scholar Program. [emphases mine]

This is an image you’ll find in the abstract for the 2019 paper,

[downloaded from https://pubs.acs.org/doi/10.1021/acssynbio.8b00381]

Here are links and citations for the 2018 papers and the 2019 paper,

BioBits™ Explorer: A modular synthetic biology education kit by Ally Huang, Peter Q. Nguyen, Jessica C. Stark, Melissa K. Takahashi, Nina Donghia, Tom Ferrante, Aaron J. Dy, Karen J. Hsu, Rachel S. Dubner, Keith Pardee, Michael C. Jewett, and James J. Collins. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5105 DOI: 10.1126/sciadv.aat5105

BioBits™ Bright: A fluorescent synthetic biology education kit by Jessica C. Stark, Ally Huang, Peter Q. Nguyen, Rachel S. Dubner, Karen J. Hsu, Thomas C. Ferrante, Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica S. Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Thomas Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander R. Hill, Jemima F. Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzalzles, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, TaRhonda Woods, Nina Donghia, Keith Pardee, James J. Collins, and Michael C. Jewett. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5107 DOI: 10.1126/sciadv.aat5107

BioBits Health: Classroom Activities Exploring Engineering, Biology, and Human Health with Fluorescent Readouts by Jessica C. Stark, Ally Huang, Karen J. Hsu, Rachel S. Dubner, Jason Forbrook, Suzanne Marshalla, Faith Rodriguez, Mechelle Washington, Grant A. Rybnicky, Peter Q. Nguyen, Brenna Hasselbacher, Ramah Jabri, Rijha Kamran, Veronica Koralewski, Will Wightkin, Thomas Martinez, and Michael C. Jewett. ACS Synth. Biol., Article ASAP
DOI: 10.1021/acssynbio.8b00381 Publication Date (Web): March 29, 2019

Copyright © 2019 American Chemical Society

Both of the 2018 papers appear to be open access while the 2019 paper is behind a paywall.

Should you be interested in acquiring a BioBits kit, you can check out the BioBits website. As for ‘conguering’ CRISPR, do we really need to look at it that way? Maybe a more humble appraoch could work just as well or even better, eh?

*’is’ removed from sentence on May 9, 2019.

Altered virus spins gold into beads

They’re not calling this synthetic biology but I’ m pretty sure that altering a virus gene so the virus can spin gold (Rumpelstiltskin anyone?) qualifies. From an August 24, 2018 news item on ScienceDaily,

The race is on to find manufacturing techniques capable of arranging molecular and nanoscale objects with precision.

Engineers at the University of California, Riverside, have altered a virus to arrange gold atoms into spheroids measuring a few nanometers in diameter. The finding could make production of some electronic components cheaper, easier, and faster.

An August 23, 2018 University of California at Riverside (UCR) news release (also on EurekAlett) by Holly Ober, which originated the news item, adds detail,

“Nature has been assembling complex, highly organized nanostructures for millennia with precision and specificity far superior to the most advanced technological approaches,” said Elaine Haberer, a professor of electrical and computer engineering in UCR’s Marlan and Rosemary Bourns College of Engineering and senior author of the paper describing the breakthrough. “By understanding and harnessing these capabilities, this extraordinary nanoscale precision can be used to tailor and build highly advanced materials with previously unattainable performance.”

Viruses exist in a multitude of shapes and contain a wide range of receptors that bind to molecules. Genetically modifying the receptors to bind to ions of metals used in electronics causes these ions to “stick” to the virus, creating an object of the same size and shape. This procedure has been used to produce nanostructures used in battery electrodes, supercapacitors, sensors, biomedical tools, photocatalytic materials, and photovoltaics.

The virus’ natural shape has limited the range of possible metal shapes. Most viruses can change volume under different scenarios, but resist the dramatic alterations to their basic architecture that would permit other forms.

The M13 bacteriophage, however, is more flexible. Bacteriophages are a type of virus that infects bacteria, in this case, gram-negative bacteria, such as Escherichia coli, which is ubiquitous in the digestive tracts of humans and animals. M13 bacteriophages genetically modified to bind with gold are usually used to form long, golden nanowires.

Studies of the infection process of the M13 bacteriophage have shown the virus can be converted to a spheroid upon interaction with water and chloroform. Yet, until now, the M13 spheroid has been completely unexplored as a nanomaterial template.

Haberer’s group added a gold ion solution to M13 spheroids, creating gold nanobeads that are spiky and hollow.

“The novelty of our work lies in the optimization and demonstration of a viral template, which overcomes the geometric constraints associated with most other viruses,” Haberer said. “We used a simple conversion process to make the M13 virus synthesize inorganic spherical nanoshells tens of nanometers in diameter, as well as nanowires nearly 1 micron in length.”

The researchers are using the gold nanobeads to remove pollutants from wastewater through enhanced photocatalytic behavior.

The work enhances the utility of the M13 bacteriophage as a scaffold for nanomaterial synthesis. The researchers believe the M13 bacteriophage template transformation scheme described in the paper can be extended to related bacteriophages.

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

M13 bacteriophage spheroids as scaffolds for directed synthesis of spiky gold nanostructures by Tam-Triet Ngo-Duc, Joshua M. Plank, Gongde Chen, Reed E. S. Harrison, Dimitrios Morikis, Haizhou Liu, and Elaine D. Haberer. Nanoscale, 2018,10, 13055-13063 DOI: 10.1039/C8NR03229G First published on 25 Jun 2018

This paper is behind a paywall.

For another example of genetic engineering and synthetic biology, see my July 18, 2018 posting: Genetic engineering: an eggplant in Bangladesh and a synthetic biology grant at Concordia University (Canada).

For anyone unfamiliar with the Rumpelstiltskin fairytale about spinning straw into gold, see its Wikipedida entry.

Call for abstracts: Seventh annual conference on governance of emerging technologies & science (GETS)

The conference itself will be held from May 22 – 24, 2019 at Arizona State University (ASU) and the deadline for abstracts is January 31, 2019. Here’s the news straight from the January 8, 2019 email announcement,

The Seventh Annual Conference on Governance of Emerging Technologies & Science (GETS)

May 22-24, 2019 / ASU / Sandra Day O’Connor College of Law
111 E. Taylor St., Phoenix, AZ
 
The conference will consist of plenary and session presentations and discussions on regulatory, governance, legal, policy, social and ethical aspects of emerging technologies, including nanotechnology, synthetic biology, gene editing, biotechnology, genomics, personalized medicine, digital health, human enhancement, artificial intelligence, virtual reality, internet of things (IoT), blockchain and much, much more!
 
Submit Your Abstract Here: 2019 Abstract
or
Conference Website
 
Call for abstracts:
 
The co-sponsors invite submission of abstracts for proposed presentations. Submitters of abstracts need not provide a written paper, although provision will be made for posting and possible post-conference publication of papers for those who are interested. 
Abstracts are invited for any aspect or topic relating to the governance of emerging technologies, including any of the technologies listed above.
 
·         Abstracts should not exceed 500 words and must contain your name and email address.
·         Abstracts must be submitted by January 31, 2019 to be considered. 
·         The sponsors will pay for the conference registration (including all conference meals and events) for one presenter for each accepted abstract. In addition, we will have limited funds available for travel subsidies (application included in submission form).
For more informationcontact our Executive Director Josh Abbott at Josh.Abbott@asu.edu.

Good luck on your submission!

Café Scientifique Vancouver (Canada) talk on October 30th, 2018: Solving some of Canada’s grandest challenges with synthetic biology

From an October 16, 2018 Café Scientifique Vancouver announcement (received via email),

Our next café will happen on TUESDAY, OCTOBER 30TH at 7:30PM in the
back room at YAGGER’S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. VIKRAMADITYA G. YADAV. His topic will be:

SOLVING SOME OF CANADA’S GRANDEST CHALLENGES WITH SYNTHETIC BIOLOGY

A warming climate, unrepressed mining and logging, contamination of our
water resources, the uncertain price and tight supply of crude oil and
the growing threat of epidemics are having a profound, negative impact
on the well-being of Canadians. There is an urgent need to develop and
implement sustainable manufacturing technologies that can not only meet
our material and energy needs, but also sustain our quality of life.
Romantic and unbelievable as it sounds, Nature posses all the answer to
our challenges, and the coming decades in science and engineering will
be typified by our attempts to mimic or recruit biology to address our
needs. This talk will present a vivid snapshot of current and emerging
research towards this goal and highlight some cutting-edge technologies
under development at the University of British Columbia [UBC].

When he joined the University of Waterloo as an undergraduate student in
chemical engineering, Dr. Vikramaditya G. Yadav coveted a career in
Alberta’s burgeoning petrochemical sector. He even interned at Imperial
Oil during his first summer break from university. Then, one fine
evening during second year, he stumbled upon a copy of Juan Enríquez’s
As the Future Catches You in the library and became instantly captivated
with biological engineering. His journey over the past few years has
taken him to Sanofi Pasteur [vaccines division of the multinational
pharmaceutical
company Sanofi], the Massachusetts Institute of Technology [MIT],
Harvard University, and finally, the University of British Columbia,
where he now leads a wonderful group of researchers working on
wide-ranging topics at the interface of biology, chemistry, engineering,
medicine and economics.

We hope to see you there!

Oftentimes, the speaker is asked to write up a description of their talk and assuming that’s the case and based on how it’s written, I’d say the odds are good that this will be a lively, engaging talk.

For more proof, you can check out Dr. Yadav’s description of his research interests on his UBC profile page. BTW, his research group is called The Biofoundry (at UBC).

Genetic engineering: an eggplant in Bangladesh and a synthetic biology grant at Concordia University (Canada)

I have two bits of genetic engineering news.

Eggplants in Bangladesh

I always marvel at their beauty,

Bt eggplant is the first genetically engineered food crop to be successfully introduced in South Asia. The crop is helping some of the world’s poorest farmers feed their families and communities while reducing the use of pesticides. Photo by Cornell Alliance for Science.

A July 17, 2018 news item on phys.org describes a genetic engineering application,

Ansar Ali earned just 11,000 taka – about $130 U.S. dollars – from eggplant he grew last year in Bangladesh. This year, after planting Bt eggplant, he brought home more than double that amount, 27,000 taka. It’s a life-changing improvement for a subsistence farmer like Ali.

Bt eggplant, or brinjal as it’s known in Bangladesh, is the first genetically engineered food crop to be successfully introduced in South Asia. Bt brinjal is helping some of the world’s poorest farmers to feed their families and communities, improve profits and dramatically reduce pesticide use. That’s according to Tony Shelton, Cornell professor of entomology and director of the Bt brinjal project funded by the United States Agency for International Development (USAID). Shelton and Jahangir Hossain, the country coordinator for the project in Bangladesh, lead the Cornell initiative to get these seeds into the hands of the small-scale, resource-poor farmers who grow a crop consumed daily by millions of Bangladeshis.

A July 11, 2018 Cornell University news release by Krisy Gashler, which originated the news item, expands on the theme (Note: Links have been removed),

Bt brinjal was first developed by the Indian seed company Mahyco in the early 2000s. Scientists inserted a gene from the bacterium Bacillus thuringiensis (thus the name, Bt) into nine brinjal varieties. The plants were engineered to resist the fruit and shoot borer, a devastating insect whose larvae bore into the stem and fruit of an eggplant. The insects cause up to 80 percent crop loss.

The Bt protein produced by the engineered eggplant causes the fruit and shoot borer larva to stop feeding, but is safe for humans consuming the eggplant, as proven through years of biosafety trials. In fact, Bt is commonly used by organic farmers to control caterpillars but has to be sprayed frequently to be effective. The Bt eggplant produces essentially the same protein as in the spray. More than 80 percent of field corn and cotton grown in the U.S. contains a Bt gene for insect control.

“Farmers growing Bt brinjal in Bangladesh are seeing three times the production of other brinjal varieties, at half the production cost, and are getting better prices at the market,” Hossain said.

A recent survey found 50 percent of farmers in Bangladesh said that they experienced illness due to the intense spraying of insecticides. Most farmers work in bare feet and without eye protection, leading to pesticide exposure that causes skin and eye irritation, and vomiting.

“It’s terrible for these farmers’ health and the health of the environment to spray so much,” said Shelton, who found that pesticide use on Bt eggplant was reduced as much as 92 percent in commercial Bt brinjal plantings. “Bt brinjal is a solution that’s really making a difference in people’s lives.”

Alhaz Uddin, a farmer in the Tangail district, made 6,000 taka growing traditional brinjal, but had to spend 4,000 taka on pesticides to combat fruit and shoot borer.

“I sprayed pesticides several times in a week,” he said. “I got sick many times during the spray.”

Mahyco initially wanted to introduce Bt brinjal in India and underwent years of successful safety testing. But in 2010, due to pressure from anti-biotechnology groups, the Indian minister of the environment placed a moratorium on the seeds. It is still in effect today, leaving brinjal farmers there without the effective and safe method of control available to their neighbors in Bangladesh.

Even before the Indian moratorium, Cornell scientists hosted delegations from Bangladesh that wanted to learn about Bt brinjal and the Agricultural Biotechnology Support Project II (ABSP II), a consortium of public and private institutions in Asia and Africa intended to help with the commercial development, regulatory approval and dissemination of bio-engineered crops, including Bt brinjal.

Cornell worked with USAID, Mahyco and the Bangladesh Agricultural Research Institute to secure regulatory approval, and in 2014 the Bangladeshi government distributed a small number of Bt brinjal plants to 20 farmers in four districts. The next year 108 farmers grew Bt brinjal, and the following year the number of farmers more than doubled to 250. In 2017 the number increased to 6,512 and in 2018 to 27,012. The numbers are likely even higher, according to Shelton, as there are no constraints against farmers saving seeds and replanting.

“Farmers who plant Bt brinjal are required to plant a small perimeter of traditional brinjal around the Bt variety; research has shown that the insects will infest plants in the buffer area, and this will slow their evolutionary development of resistance to the Bt plants,” Shelton said.

In a March 2017 workshop, Bangladeshi Agriculture Minister Begum Matia Chowdhury called Bt brinjal “a success story of local and foreign collaboration.”

“We will be guided by the science-based information, not by the nonscientific whispering of a section of people,” Chowdhury said. “As human beings, it is our moral obligation that all people in our country should get food and not go to bed on an empty stomach. Biotechnology can play an important role in this effect.”

Here’s what an infested eggplant looks like,

Non-Bt eggplant infested with fruit and shoot borer. Photo by Cornell Alliance for Science

It looks more like a fig than an eggplant.

This is part of a more comprehensive project as revealed in a March 29, 2016 Cornell University news release issued on the occasion of a $4.8M, three-year grant from the U.S. Agency for International Development (USAID),

… The award supports USAID’s work under Feed the Future, the U.S. government’s global initiative to fight hunger and improve food security using agricultural science and technology.

In the Feed the Future South Asia Eggplant Improvement Partnership, Cornell will protect eggplant farmers from yield losses and improve their livelihoods in partnership with the Bangladesh Agricultural Research Institute (BARI) and the University of the Philippines at Los Baños. Eggplant, or brinjal, is a staple crop that is an important source of income and nutrition for farmers and consumers in South Asia.

Over the past decade, Cornell has led the Agricultural Biotechnology Support Project II (ABSPII), also funded by USAID, that prompted a consortium of institutions in Asia and Africa to use the tools of modern biotechnology, particularly genetic engineering, to improve crops to address major production constraints for which conventional plant breeding tools have not been effective.

In October 2013, Bangladesh became the first country in South Asia to approve commercial cultivation of a genetically engineered food crop. In February 2014, Matia Chowdhury, the Bangladesh minister of agriculture, released four varieties of Bt brinjal to 20 farmers. With the establishment of the 20 Bt brinjal demonstration plots in 2014 and 104 more in 2015, BARI reported a noticeable decrease in fruit and shoot borer infestation, increased yields, decreased use of pesticide and improved income for farmers.

The Feed the Future South Asia Eggplant Improvement Partnership addresses and integrates all elements of the commercialization process — including technology development, regulation, marketing, seed distribution, and product stewardship. It also provides strong platforms for policy development, capacity building, gender equality, outreach and communication.

Moving on from practical applications …

Canada’s synthetic biology training centre

It seems Concordia University (Montréa) is a major Canadian centre for all things ‘synthetic biological’. (from the History and Vision webpage on Concordia University’s Centre for Applied Synthetic Biology webspace),

History and vision

Emerging in 2012 from a collaboration between the Biology and Electrical and Computer Engineering Departments, the Centre received University-wide status in 2016 growing its membership to include Biochemistry, Journalism, Communication Studies, Mechanical, Industrial and Chemical Engineering.


Timeline

T17-36393-VPRG-Timeline-graphic-promo-v4

You can see the timeline does not yet include 2018 development(s). Also it started as “a collaboration between the Biology and Electrical and Computer Engineering Departments?” This suggests a vastly different approach to genetic engineering that that employed in the “eggplant” research. From a July 16, 2018 posting on the Genome Alberta blog,

The Natural Sciences and Engineering Research Council of Canada (NSERC) has committed $1.65 million dollars over six years to establish a research and training program at Concordia’s Centre for Applied Synthetic Biology.

The funds were awarded after Malcolm Whiteway (…), professor of biology and the Canada Research Chair in Microbial Genomics, and the grant application team submitted a proposal to NSERC’s Collaborative Research and Training Experience (CREATE) program.

The Synthetic Biology Applications CREATE program — or SynBioApps — will help students acquire and develop important professional skills that complement their academic education and improve their job-readiness.

‘Concordia is a natural fit’

“As the Canadian leader in synthetic biology and as the home of the country’s only genome foundry, Concordia is a natural fit for a training program in this growing area of research,” says Christophe Guy, vice-president of Research and Graduate Studies.

“In offering a program like SynBioApps, we are providing our students with both a fundamental education in science and the business skills they’ll need to transition into their professional careers.”

The program’s aims are twofold: First, it will teach students how to design and construct cells and proteins for the development of new products related to human health, green technologies, and fundamental biological investigations. Second, it will provide cross-disciplinary training and internship opportunities through the university’s District 3 Innovation Center.

SynBioApps will be open to students from biology, biochemistry, engineering, computing, and mathematics.

“The ability to apply engineering approaches to biological systems promises to revolutionize both biology and industry,” says Whiteway, who is also a member of the Centre for Applied Synthetic Biology.

“The SynBioApps program at Concordia will provide a training program to develop the students who will both investigate the biology and build these industries.”

You can find out more about Concordia’s Centre for Applied Synthetic Biology here (there are jobs listed on their home page) and you can find information about the Synthetic Biology Applications (SynBioApps) training programme here.

The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle

Setting the stage

Not unexpectedly, CRISPR-Cas9  or clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 can be dangerous as these scientists note in a July 16, 2018 news item on phys.org,

Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.

Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.

This CRISPR-Cas9 image reminds me of popcorn,

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)[ downloaded from https://phys.org/news/2018-07-genome-crisprcas9-gene-higher-thought.html#jCp]

A July 16, 2018 Wellcome Sanger Institute press release (also on EurekAlert), which originated the news item, offers a little more explanation,

CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.

Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.

The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.

Prof Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said: “This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects.”

Michael Kosicki, the first author from the Wellcome Sanger Institute, said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

Prof Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study said: “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”

For anyone who’d like to better understand the terms gene editing and CRISPR-Cas9, the Wellcome Sanger Institute provides these explanatory webpages, What is genome editing? and What is CRISPR-Cas9?

For the more advanced, here’s a link and a citation for the paper,

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements by Michael Kosicki, Kärt Tomberg, & Allan Bradley. Nature Biotechnology DOI: https://doi.org/10.1038/nbt.4192 Published 16 July 2018

This paper appears to be open access.

The kerfuffle

It seems this news has affected the CRISPR market. From a July 16, 2018 article by Cale Guthrie Weissman for Fast Company,

… CRISPR could unknowingly delete or alter non-targeted genes, which could lead to myriad unintended consequences. This is especially frightening, since the technology is going to be used in human clinical trials.

Meanwhile, other scientists working with CRISPR are trying to downplay the findings, telling STAT [a life sciences and business journalism website] that there have been no reported adverse effects similar to what the study describes. The news, however, has brought about a market reaction–at least three publicly traded companies that focus on CRISPR-based therapies are in stock nosedive. Crispr Therapeutics is down by over 6%; Editas fell by over 3%; and Intellia Therapeutics dropped by over 5%. [emphasis mine]

Damage control

Gaetan Burgio (geneticist, Australian National University)  in a July 16, 2018 essay on phys.org (originating from The Conversation) suggests some calm (Note: Links have been removed),

But a new study has called into question the precision of the technique [CRISPR gene editing technology].

The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing deafness in mice, and in altering cells to cure cancer.

Some 17 clinical trials in human patients are registered [emphasis mine] testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.

There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.

For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.

While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.

Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).

As RNA [ribonucleic acid] remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time).

This was found to be successful for dementia in mice. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as hereditary deafness in mice.

I agree with Burgio’s conclusion (not included here) that we have a lot more to learn and I can’t help wondering why there are 17 registered human clinical trials at this point.

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) .

Book commentaries: The Science of Orphan Black: The Official Companion and Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive

I got more than I expected from both books (“The Science of Orphan Black: The Official Companion” by Casey Griffin and Nina Nesseth and “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive” by Ethan Siegel) I’m going to discuss by changing my expectations.

The Science of Orphan Black: The Official Companion

I had expected a book about the making of the series with a few insider stories about the production along with some science. Instead, I was treated to a season by season breakdown of the major scientific and related ethical issues in the fields of cloning and genetics.I don’t follow those areas exhaustively but from my inexpert perspective, the authors covered everything I could have hoped for (e.g., CRISPR/CAS9, Henrietta Lacks, etc.) in an accessible but demanding writing style  In other words, it’s a good read but it’s not a light read.

There are many, many pictures of Tatiana Maslany as one of her various clone identities in the book. Unfortunately, the images do not boast good reproduction values. This was disconcerting as it can lead a reader (yes, that was me) to false expectations (e.g., this is a picture book) concerning the contents. The boxed snippets from the scripts and explanatory notes inset into the text helped to break up some of the more heavy going material while providing additional historical/scripting/etc. perspectives. One small niggle, the script snippets weren’t always as relevant to the discussion at hand as the authors no doubt hoped.

I suggest reading both the Foreword by Cosima Herter, the series science consultant, and (although it could have done with a little editing) The Conversation between Cosima Herter and Graeme Manson (one of the producers). That’s where you’ll find that the series seems to have been incubated in Vancouver, Canada. It’s also where you’ll find out how much of Cosima Herter’s real life story is included in the Cosima clone’s life story.

The Introduction tells you how the authors met (as members of ‘the clone club’) and started working together as recappers for the series. (For anyone unfamiliar with the phenomenon or terminology, episodes of popular series are recapitulated [recapped] on one or more popular websites. These may or may not be commercial, i.e., some are fan sites.)

One of the authors, Casey Griffin, is a PhD candidate at the University of Southern California (USC) studying in the field of developmental and stem cell biology. I was not able to get much more information but did find her LinkedIn profile. The other author also has a science background. Nina Nesseth is described as a science communicator on the back cover of the book but she’s described as a staff scientist for Science North, a science centre located in Sudbury, Ontario, Canada. Her LinkedIn profile lists an honours Bachelor of Science (Biological and Medical Sciences) from Laurentian University, also located in Sudbury, Ontario.

It’s no surprise, given the authors’ educational background, that a bibliography (selected) has been included. This is something I very much appreciated. Oddly, given that Nesseth lists a graduate certificate in publishing as one of her credentials (on LinkedIn), there is no index (!?!). Unusually, the copyright page is at the back of the book instead of the front and boasts a fairly harsh copyright notice (summary: don’t copy anything, ever … unless you get written permission from ECW Press and the other copyright owners; Note: Herter is the copyright owner of her Foreword while the authors own the rest).

There are logos on the copyright page—more than I’m accustomed to seeing. Interestingly, two of them are government logos. It seems that taxpayers contributed to the publication of this book. The copyright notice seems a little facey to me since taxpayers (at least partially) subsidized the book, as well, Canadian copyright law has a concept called fair dealing (in the US, there’s something similar: fair use). In other words, if I chose, I could copy portions of the text without asking for permission if there’s no intent to profit from it and as long as I give attributions.

How, for example, could anyone profit from this?

In fact, in January 2017, Jun Wu and colleagues published their success in creating pig-human hybrids. (description of real research on chimeras on p. 98)

Or this snippet of dialogue,

[Charlotte] You’re my big sister.

[Sarah] How old are you? (p. 101)

All the quoted text is from “The Science of Orphan Black: The Official Companion” by Casey Griffin and Nina Nesseth (paperback published August 22, 2017).

On the subject of chimeras, the Canadian Broadcasting Corporation (CBC) featured a January 26, 2017 article about the pig-human chimeras on its website along with a video,

Getting back to the book, copyright silliness aside, it’s a good book for anyone interested in some of the  science and the issues associated with biotechnology, synthetic biology, genomes, gene editing technologies, chimeras, and more. I don’t think you need to have seen the series in order to appreciate the book.

Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive

This looks and feels like a coffee table book. The images in this book are of a much higher quality than those in the ‘Orphan Black’ book. With thicker paper and extensive ink coverage lending to its glossy, attractive looks, it’s a physically heavy book. The unusually heavy use of black ink  would seem to be in service of conveying the feeling that you are exploring the far reaches of outer space.

It’s clear that “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive’s” author, Ethan Siegel, PhD., is a serious Star Trek and space travel fan. All of the series and movies are referenced at one time or another in the book in relationship to technology (treknology).

Unlike Siegel, while I love science fiction and Star Trek, I have never been personally interested in space travel. Regardless, Siegel did draw me in with his impressive ability to describe and explain physics-related ideas. Unfortunately, his final chapter on medical and biological ‘treknology’ is not as good. He covers a wide range of topics but no one is an expert on everything.

Siegel has a Wikipedia entry, which notes this (Note: Links have been removed),

Ethan R. Siegel (August 3, 1978, Bronx)[1] is an American theoretical astrophysicist and science writer, who studies Big Bang theory. He is a professor at Lewis & Clark College and he blogs at Starts With a Bang, on ScienceBlogs and also on Forbes.com since 2016.

By contrast with the ‘Orphan Black’ book, the tone is upbeat. It’s one of the reasons Siegel appreciates Star Trek in its various iterations,

As we look at the real-life science and technology behind the greatest advances anticipated by Star Trek, it’s worth remembering that the greatest legacy of the show is its message of hope. The future can be brighter and better than our past or present has ever been. It’s our continuing mission to make it so. (p. 6)

All the quoted text is from “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive” by Ethan Siegel (hard cover published October 15, 2017).

This book too has one of those copyright notices that fail to note you don’t need permission when it’s fair dealing to copy part of the text. While it does have an index, it’s on the anemic side and, damningly, there are neither bibliography nor reference notes of any sort. If Siegel hadn’t done such a good writing job, I might not have been so distressed.

For example, it’s frustrating for someone like me who’s been trying to get information on cortical/neural  implants and finds this heretofore unknown and intriguing tidbit in Siegel’s text,

In 2016, the very first successful cortical implant into a patient with ALS [amyotrophic lateral sclerosis] was completed, marking the very first fully implanted brain-computer interface in a human being. (p. 180)

Are we talking about the Australia team, which announced human clinical trials for their neural/cortical implant (my February 15, 2016 posting) or was it preliminary work by a team in Ohio (US) which later (?) announced a successful implant for a quadriplegic (also known as tetraplegic) patient who was then able to move hands and fingers (see my April 19, 2016 posting)? Or is it an entirely different team?

One other thing, I was a bit surprised to see no mention of quantum or neuromorphic computing in the chapter on computing. I don’t believe either was part of the Star Trek universe but they (neuromorphic and quantum computing) are important developments and Siegel makes a point, on at least a few occasions, of contrasting present day research with what was and wasn’t ‘predicted’ by Star Trek.

As for the ‘predictions’, there’s a longstanding interplay between storytellers and science and sometimes it can be a little hard to figure out which came first. I think Siegel might have emphasized that give and take a bit more.

Regardless of my nitpicking, Siegel is a good writer and managed to put an astonishing amount of ‘educational’ material into a lively and engaging book. That is not easy.

Final thoughts

I enjoyed both books and am very excited to see grounded science being presented along with the fictional stories of both universes (Star Trek and Orphan Black).

Yes, both books have their shortcomings (harsh copyright notices, no index, no bibliography, no reference notes, etc.) but in the main they offer adults who are sufficiently motivated a wealth of current scientific and technical information along with some elucidation of ethical issues.

Why don’t you CRISPR yourself?

It must have been quite the conference. Josiah Zayner plunged a needle into himself and claimed to have changed his DNA (deoxyribonucleic acid) while giving his talk. (*Segue: There is some Canadian content if you keep reading.*) From an Oct. 10, 2017 article by Adele Peters for Fast Company (Note: A link has been removed),

“What we’ve got here is some DNA, and this is a syringe,” Josiah Zayner tells a room full of synthetic biologists and other researchers. He fills the needle and plunges it into his skin. “This will modify my muscle genes and give me bigger muscles.”

Zayner, a biohacker–basically meaning he experiments with biology in a DIY lab rather than a traditional one–was giving a talk called “A Step-by-Step Guide to Genetically Modifying Yourself With CRISPR” at the SynBioBeta conference in San Francisco, where other presentations featured academics in suits and the young CEOs of typical biotech startups. Unlike the others, he started his workshop by handing out shots of scotch and a booklet explaining the basics of DIY [do-it-yourwelf] genome engineering.

If you want to genetically modify yourself, it turns out, it’s not necessarily complicated. As he offered samples in small baggies to the crowd, Zayner explained that it took him about five minutes to make the DNA that he brought to the presentation. The vial held Cas9, an enzyme that snips DNA at a particular location targeted by guide RNA, in the gene-editing system known as CRISPR. In this case, it was designed to knock out the myostatin gene, which produces a hormone that limits muscle growth and lets muscles atrophy. In a study in China, dogs with the edited gene had double the muscle mass of normal dogs. If anyone in the audience wanted to try it, they could take a vial home and inject it later. Even rubbing it on skin, Zayner said, would have some effect on cells, albeit limited.

Peters goes on to note that Zayner has a PhD in molecular biology and biophysics and worked for NASA (US National Aeronautics and Space Administration). Zayner’s Wikipedia entry fills in a few more details (Note: Links have been removed),

Zayner graduated from the University of Chicago with a Ph.D. in biophysics in 2013. He then spent two years as a researcher at NASA’s Ames Research Center,[2] where he worked on Martian colony habitat design. While at the agency, Zayner also analyzed speech patterns in online chat, Twitter, and books, and found that language on Twitter and online chat is closer to how people talk than to how they write.[3] Zayner found NASA’s scientific work less innovative than he expected, and upon leaving in January 2016, he launched a crowdfunding campaign to provide CRISPR kits to let the general public experiment with editing bacterial DNA. He also continued his grad school business, The ODIN, which sells kits to let the general public experiment at home. As of May 2016, The ODIN had four employees and operates out of Zayner’s garage.[2]

He refers to himself as a biohacker and believes in the importance in letting the general public participate in scientific experimentation, rather than leaving it segregated to labs.[2][4][1] Zayner found the biohacking community exclusive and hierarchical, particularly in the types of people who decide what is “safe”. He hopes that his projects can let even more people experiment in their homes. Other scientists responded that biohacking is inherently privileged, as it requires leisure time and money, and that deviance from the safety rules of concern would lead to even harsher regulations for all.[5] Zayner’s public CRISPR kit campaign coincided with wider scrutiny over genetic modification. Zayner maintained that these fears were based on misunderstandings of the product, as genetic experiments on yeast and bacteria cannot produce a viral epidemic.[6][7] In April 2015, Zayner ran a hoax on Craigslist to raise awareness about the future potential of forgery in forensics genetics testing.[8]

In February 2016, Zayner performed a full body microbiome transplant on himself, including a fecal transplant, to experiment with microbiome engineering and see if he could cure himself from gastrointestinal and other health issues. The microbiome from the donors feces successfully transplanted in Zayner’s gut according to DNA sequencing done on samples.[2] This experiment was documented by filmmakers Kate McLean and Mario Furloni and turned into the short documentary film Gut Hack.[9]

In December 2016, Zayner created a fluorescent beer by engineering yeast to contain the green fluorescent protein from jellyfish. Zayner’s company, The ODIN, released kits to allow people to create their own engineered fluorescent yeast and this was met with some controversy as the FDA declared the green fluorescent protein can be seen as a color additive.[10] Zayner, views the kit as a way that individual can use genetic engineering to create things in their everyday life.[11]

I found the video for Zayner’s now completed crowdfunding campaign,

I also found The ODIN website (mentioned in the Wikipedia essay) where they claim to be selling various gene editing and gene engineering kits including the CRISPR editing kits mentioned in Peters’ article,

In 2016, he [Zayner] sold $200,000 worth of products, including a kit for yeast that can be used to brew glowing bioluminescent beer, a kit to discover antibiotics at home, and a full home lab that’s roughly the cost of a MacBook Pro. In 2017, he expects to double sales. Many kits are simple, and most buyers probably aren’t using the supplies to attempt to engineer themselves (many kits go to classrooms). But Zayner also hopes that as people using the kits gain genetic literacy, they experiment in wilder ways.

Zayner sells a full home biohacking lab that’s roughly the cost of a MacBook Pro. [Photo: The ODIN]

He questions whether traditional research methods, like randomized controlled trials, are the only way to make discoveries, pointing out that in newer personalized medicine (such as immunotherapy for cancer, which is personalized for each patient), a sample size of one person makes sense. At his workshop, he argued that people should have the choice to self-experiment if they want to; we also change our DNA when we drink alcohol or smoke cigarettes or breathe in dirty city air. Other society-sanctioned activities are more dangerous. “We sacrifice maybe a million people a year to the car gods,” he said. “If you ask someone, ‘Would you get rid of cars?’–no.” …

US researchers both conventional and DIY types such as Zayner are not the only ones who are editing genes. The Chinese study mentioned in Peters’ article was written up in an Oct. 19, 2015 article by Antonio Regalado for the MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin.

The dogs have “more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications,” Liangxue Lai, a researcher with the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health, said in an e-mail.

Lai and 28 colleagues reported their results last week in the Journal of Molecular Cell Biology, saying they intend to create dogs with other DNA mutations, including ones that mimic human diseases such as Parkinson’s and muscular dystrophy. “The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research,” says Lai. “Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics.”

Lai said his group had no plans breed to breed the extra-muscular beagles as pets. Other teams, however, could move quickly to commercialize gene-altered dogs, potentially editing their DNA to change their size, enhance their intelligence, or correct genetic illnesses. A different Chinese Institute, BGI, said in September it had begun selling miniature pigs, created via gene editing, for $1,600 each as novelty pets.

People have been influencing the genetics of dogs for millennia. By at least 36,000 years ago, early humans had already started to tame wolves and shape the companions we have today. Charles Darwin frequently cited dog breeding in The Origin of Species to demonstrate how evolution gradually occurs by a process of selection. With CRISPR, however, evolution is no longer gradual or subject to chance. It is immediate and under human control.

It is precisely that power that is stirring wide debate and concern over CRISPR. Yet at least some researchers think that gene-edited dogs could put a furry, friendly face on the technology. In an interview this month, George Church, a professor at Harvard University who leads a large effort to employ CRISPR editing, said he thinks it will be possible to augment dogs by using DNA edits to make them live longer or simply make them smarter.

Church said he also believed the alteration of dogs and other large animals could open a path to eventual gene editing of people. “Germline editing of pigs or dogs offers a line into it,” he said. “People might say, ‘Hey, it works.’ ”

In the meantime, Zayner’s ideas are certainly thought provoking. I’m not endorsing either his products or his ideas but it should be noted that early science pioneers such as Humphrey Davy and others experimented on themselves. For anyone unfamiliar with Davy, (from the Humphrey Davy Wikipedia entry; Note: Links have been removed),

Sir Humphry Davy, 1st Baronet PRS MRIA FGS (17 December 1778 – 29 May 1829) was a Cornish chemist and inventor,[1] who is best remembered today for isolating a series of substances for the first time: potassium and sodium in 1807 and calcium, strontium, barium, magnesium and boron the following year, as well as discovering the elemental nature of chlorine and iodine. He also studied the forces involved in these separations, inventing the new field of electrochemistry. Berzelius called Davy’s 1806 Bakerian Lecture On Some Chemical Agencies of Electricity[2] “one of the best memoirs which has ever enriched the theory of chemistry.”[3] He was a Baronet, President of the Royal Society (PRS), Member of the Royal Irish Academy (MRIA), and Fellow of the Geological Society (FGS). He also invented the Davy lamp and a very early form of incandescent light bulb.

Canadian content*

A Nov. 11, 2017 posting on the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks blog notes that self-experimentation has a long history and goes on to describe Zayner’s and others biohacking exploits before describing the legality of biohacking in Canada,

With biohackers entering into the space traditionally held by scientists and clinicians, it begs questions. Professor Timothy Caulfield, a Canada research chair in health, law and policy at the University of Alberta, says when he hears of somebody giving themselves biohacked gene therapy, he wonders: “Is this legal? Is this safe? And if it’s not safe, is there anything that we can do about regulating it? And to be honest with you that’s a tough question and I think it’s an open question.”

In Canada, Caulfield says, Health Canada focuses on products. “You have to have something that you are going to regulate or you have to have something that’s making health claims. So if there is a product that is saying I can cure X, Y, or Z, Health Canada can say, ‘Well let’s make sure the science really backs up that claim.’ The problem with these do-it-yourself approaches is there isn’t really a product. You know these people are experimenting on themselves with something that may or may not be designed for health purposes.”

According to Caufield, if you could buy a gene therapy kit that was being marketed to you to biohack yourself, that would be different. “Health Canada could jump in. But right here that’s not the case,” he says.

There are places in the world that do regulate biohacking, says Caulfield. “Germany, for example, they have specific laws for it. And here in Canada we do have a regulatory framework that says that you cannot do gene therapy that will alter the germ line. In other words, you can’t do gene therapy or any kind of genetic editing that will create a change that you will pass on to your offspring. So that would be illegal, but that’s not what’s happening here. And I don’t think there’s a regulatory framework that adequately captures it.”

Infectious disease and policy experts aren’t that concerned yet about the possibility of a biohacker unleashing a genetically modified super germ into the population.

“I think in the future that could be a problem,”says Caulfield, “but this isn’t something that would be easy to do in your garage. I think it’s complicated science. But having said that, the science is moving quickly. We need to think about how we are going to control the potential harms.”

You can find out more about the ‘wild’ people (mostly men) of early science in Richard Holmes’ 2008 book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science.

Finally, should you be interested in connecting with synthetic biology enthusiasts, entrepreneurs, and others, SynBioBeta is more than a conference; it’s also an activity hub.

ETA January 25, 2018 (five minutes later): There are some CRISPR/CAS9 events taking place in Toronto, Canada on January 24 and 25, 2018. One is a workshop with Portuguese artist, Marta de Menezes, and the other is a panel discussion. See my January 10, 2018 posting for more details.

*’Segue: There is some Canadian content if you keep reading.’ and ‘Canadian content’ added January 25, 2018 six minutes after first publication.

ETA February 20, 2018: Sarah Zhang’s Feb. 20, 2018 article for The Atlantic revisits Josiah Zayner’s decision to inject himself with CRISPR,

When Josiah Zayner watched a biotech CEO drop his pants at a biohacking conference and inject himself with an untested herpes treatment, he realized things had gone off the rails.

Zayner is no stranger to stunts in biohacking—loosely defined as experiments, often on the self, that take place outside of traditional lab spaces. You might say he invented their latest incarnation: He’s sterilized his body to “transplant” his entire microbiome in front of a reporter. He’s squabbled with the FDA about selling a kit to make glow-in-the-dark beer. He’s extensively documented attempts to genetically engineer the color of his skin. And most notoriously, he injected his arm with DNA encoding for CRISPR that could theoretically enhance his muscles—in between taking swigs of Scotch at a live-streamed event during an October conference. (Experts say—and even Zayner himself in the live-stream conceded—it’s unlikely to work.)

So when Zayner saw Ascendance Biomedical’s CEO injecting himself on a live-stream earlier this month, you might say there was an uneasy flicker of recognition.

“Honestly, I kind of blame myself,” Zayner told me recently. He’s been in a soul-searching mood; he recently had a kid and the backlash to the CRISPR stunt in October [2017] had been getting to him. “There’s no doubt in my mind that somebody is going to end up hurt eventually,” he said.

Yup, it’s one of the reasons for rules; people take things too far. The trick is figuring out how to achieve balance between risk taking and recklessness.