Turning the Tide on Species Loss

2018 Year End Report

This year, Revive & Restore took a profound step forward, maturing from an ambitious startup to a catalytic conservation organization that is already making a difference. Advocating for the development of a new toolkit for conservation is an essential part of our work, but we recognize that a key barrier to the adoption of genomic solutions by the conservation community has been the lack of funding for innovative solution-oriented research. To address this issue, we are implementing select conservation projects and are excited to announce a new Catalyst Science Fund for early-stage research that will be applied towards high-impact conservation challenges.

We launched the Fund this fall to support the development of innovative genomic and biotech tools that can be applied to troubling conservation challenges like those posed by the changing climate. And, thanks to an early gift to the fund, Revive & Restore just awarded the first grant from the Catalyst Science Fund to investigate the causes of coral bleaching.

This year we were also commissioned by a new family foundation focused on “creating a more bioabundant ocean” to assess the potential application of  genomics and other biotechnology solutions. While genomic applications are still relatively limited, they hold significant potential to help solve some vexing marine conservation challenges. We are planning a major release of the report in the first quarter of 2019.

Importantly, the years of carefully planning, researching, fundraising, and collaborating have advanced our in-house genetic rescue projects to a point where important conservation outcomes are beginning to take shape. We received a first-of-its-kind permit to advance the genetic rescue of North America’s most endangered mammal, and we showed that a recombinant synthetic product can effectively stop the bleeding of half a million horseshoe crabs annually.

We would like to share with you in a little more detail the exciting advancements Revive & Restore made in 2018.

Catalyst Science Fund

A key barrier to the adoption of genomic solutions for conservation is a lack of tangible success stories. Because the use of genomics and biotechnologies to restore biodiversity is a relatively new tool, Revive & Restore has realized that a fund that strategically embraces the scientific challenges and targets cutting-edge research and development could transform conservation practice. This is the goal of the Catalyst Science Fund at Revive & Restore.

We launched the Fund with a pledge of $1 million per year for the next three years from Promega, a leading biotech company. Other donors quickly followed Promega’s lead, and the fund balance now stands at just under $4 million. The Catalyst Science Fund will support research designed to produce actionable science for the development of innovative and high-impact conservation solutions for endangered species and threatened ecosystems.

We are pleased to announce that starting in January, Bridget Baumgartner will join our team as the Catalyst Science Fund Program Manager. With a background in molecular biology and genetics, Bridget brings to this role five years of experience in program development as a contractor to the Biological Technologies Office at the Defense Advanced Research Projects Agency (DARPA), developing solutions for counteracting the impacts of climate change and reduced species diversity.  Bridget has a PhD in Cell and Molecular Biology from Baylor College of Medicine in Houston, TX and a B.S. in Biochemistry from Stony Brook University of New York. Bridget will work closely with Revive & Restore leadership and the Catalyst Fund Advisory Council to develop an overarching investment and grant strategy designed to catalyze the creation of impactful innovations in conservation.  She will work directly with the various research teams as they submit proposals, refine their scope of work, establish milestones, and oversee progress and deliverables. Establishing and growing this Catalyst Fund  will be a major focus for Revive & Restore this coming year.

First Grant Awarded to Support Innovative Coral Research

Revive & Restore is pleased to announce that our first grant from the Catalyst Science Fund has been awarded to marine biologist Steve Palumbi’s laboratory at the Stanford University Hopkins Marine Station. Made possible through the generous support of Chris Cox and Visra Vichit-Vadakan, this research will investigate the “stress trigger” that may cause corals to bleach due to warming oceans. As average sea surface temperatures around the world continue to increase, so too do the frequency and extent of global bleaching events. This means that useful interventions are crucially needed. By identifying the specific metabolic response and genetics responsible for bleaching, Palumbi’s research could transform our collective response to the global crisis of coral bleaching. Read his full proposal here.

Stanford University Marine Biologist Steve Palumbi is investigating the cause of coral bleaching.

Ocean Genomics Horizon Scan

A new foundation, founded this year to dramatically improve the health of global ocean ecosystems, commissioned Revive & Restore to explore the potential of genomic and biotechnology tools to transform marine conservation. We are preparing an “Ocean Genomics Horizon Scan” that is focused on marine conservation problems where genetic rescue and synthetic biology could be catalytic for restoring ocean health and bio-abundance. Over the course of nine months, we interviewed over 100 experts in marine biology, marine conservation, fisheries, ecology, aquaculture, genetics, synthetic biology, and genomic engineering.

These interviews reflect the emerging consensus that the pace and scale of changing ocean conditions, particularly climate change stressors, could overwhelm “traditional” conservation efforts to address threats. New forms of marine intervention are needed. The initial phase of the Horizon Scan found that, while the field is nascent, the most promising applications focus primarily on priority species like coral and particular threats like invasive species. Our Ocean Genomics Horizon Scan provides a vision and plan for the development of new approaches to address vexing marine conservation challenges. We look forward to catalyzing additional work in these areas.

Revive & Restore is building a new toolkit for marine conservation.

Horseshoe Crab

Revive & Restore traveled to Cape May, New Jersey to announce research findings that hopefully will help remove to a significant threat to this 450 million-year-old species and the migratory shorebirds that rely on their eggs for essential nutrition on their spring migrations.

Last May, when horseshoe crabs were spawning on the beaches of Delaware Bay, Revive & Restore presented the results of months of research at a press event hosted by New Jersey Audubon. We published a peer-reviewed paper demonstrating that an enzyme from recombinant DNA provides a synthetic version of a required test for bacterial contaminants that is just as effective as the test produced using the blood of the horseshoe crab. Remarkably, our research found that the if the industry used the synthetic product for just the testing of water, most companies could reduce the demand for crab blood by 90 percent. The industry can now largely eliminate the practice of bleeding 500,000 horseshoe crabs annually for biomedical testing. The timing of our paper coincided with the extraordinary efforts by the company Eli Lilly and Company to convert to the synthetic alternative in some of their manufacturing facilities. Special recognition and gratitude is due to Naira Simmons, one of the brilliant attorneys helping Revive & Restore in our pro bono agreement with Wilson Sonsini Goodrich & Rosati.

Horseshoe Crabs being bled; as much as 30% of their blood is drained during this procedure.
500,000 horseshoe crabs are bled annually, and our research is helping to eliminate the practice

Black-Footed Ferret

In July, Revive & Restore received a first-of-its-kind Endangered Species Recovery Permit from the United States Fish & Wildlife Service to initiate the genetic rescue of North America’s most endangered mammal, the black-footed ferret. All black-footed ferrets in the world today are descended from just seven individuals, which were brought into a captive breeding program in the 1980s when the species was at the verge of extinction.

Genomic sequencing sponsored by Revive & Restore revealed that, if cloned, two cell lines frozen at the San Diego Zoo would effectively represent new founders and would enhance genetic diversity. The permit authorizes Revive & Restore to conduct laboratory experiments to demonstrate the viability of cloning two frozen cell lines from ferrets stored over thirty years ago. These two individuals were part of the original captive population, but died before they could be bred.  

The permit also authorizes Revive & Restore to conduct the laboratory research for creating inheritable immunity to sylvatic plague that is fatal to black-footed ferrets. Our plan to use gene editing to up-regulate the genes that are activated by the vaccine that is currently used to protect black-footed ferrets from plague. The cloning and disease resistance work authorized under the permit can best be characterized as “proof of concept.” If successful, Revive & Restore will work on another round of federal permitting and public comment to complete the genetic rescue of the black-footed ferret.

Avian Genetic Rescue

When the Great Passenger Pigeon Comeback began in 2012, Revive & Restore had three questions: Can we bring back the Passenger Pigeon to the eastern forests of the United States? Should we do it? And if so, how do we restore them to the wild?  This year, more pieces of the big picture fell into place for both the passenger pigeon ecology and genetic engineering research.

Project Lead Ben Novak published open access research in the journal Frontiers in Ecology and Evolution: Paleoecology that shed more light on the ecologically important role played by the passenger pigeon. The study explains how reintroduced passenger pigeons would impact different types of masting oak trees inhabiting the eastern forests, information critical to designing reintroduction strategies to benefit present day forest communities.

Meanwhile, critical de-extinction research in comparative genomics and avian genome engineering is underway at Australia’s Commonwealth Scientific and Industrial Research Organization (CSIRO).

In order to discover the genes that differentiate the passenger pigeon from its closest living relative, the band-tailed pigeon, CSIRO bioinformatician Rahul Rane is comparing genomes to find mutations that make a passenger pigeon unique. But finding mutations is only the first step: discovering the specific mutation responsible for a specific trait requires testing in a living animal. For mammals, this can be done with stem cells in a petri dish, but such cellular techniques have not yet been developed in birds. Novak has been working at the CSIRO Australian Animal Health Laboratory with Tim Doran’s avian genetic engineering team to advance genetic engineering and gene editing in pigeons.

The CSIRO team hopes to create a model lab animal in which gene editing experiments can be performed in a single generation. The first step is to insert a new gene – Cas9, the enzymatic component of the CRISPR gene-editing tool – into the pigeon’s reproductive system, creating what is known as a “germ-line chimera.” When these birds are bred, their offspring will inherit the new genes.

In June, the team reached its first milestone with the hatching of its first two germ-line chimeras, a male and a female. In November, the female laid her first eggs and the team is hopeful that the world’s first genetically engineered pigeon will hatch in 2019.

Significantly, Cas9-pigeons could also expedite research for testing genetic rescue solutions for endangered birds. Specific gene editing experiments for de-extinction and genetic rescue may begin as early as 2020.

Follow @BenJNovak1 on Twitter to keep tabs on Novak’s Cas9 pigeon work.

Ben’s flock of just-weaned Cas9 germ-line chimeras. Check out the size difference between king (blue) and racer pigeon (red) breeds.

Partner News

Woolly Mammoth Revival:  
George Church and his lab at Harvard Medical School now have developed guide RNAs to edit the list of elephant genes that are different from woolly mammoth genes using bioinformatics analysis. The lab is also attempting to assemble the Elephant Herpes Virus genome from several assembled fragments, but have found that process to be more difficult than they had hoped.

In March of this year, Revive & Restore got an offer from the creators of pay-to-play smartphone game, Brutal Age, to host a donation event for the Woolly Mammoth Revival Project. Well, never look a gift mammoth in the mouth; imagine our surprise when they sent us a wire transfer of $41,853 for the Church Lab!

Stewart Brand and George Church explore an ice tunnel in Siberia’s perma-frost, which is thawing because of global warming and releasing massive amounts of methane and carbon dioxide.  If grazing megafauna can be restored to the Arctic, the thawing will be slowed, and new grasslands will draw down carbon into the soil.

Pleistocene Park:
This summer, Revive & Restore co-founder Stewart Brand, George Church and Eriona Hysolli of the Woolly Mammoth Revival Team traveled across 17 time zones to the first place on Earth that is being prepared for the de-extinction and reintroduction of the woolly mammoth, “Pleistocene Park” in far northeastern Siberia.

Sergey Zimov and his son Nikita are scientists experimenting on what it will take to restore the “mammoth steppe” grasslands of the far north. They are deploying wild Yakutian horses, musk oxen, reindeer, moose, bison, and other Arctic grazers to allow grasslands to regrow.  So far, the Zimovs have been able to clear approximately six square miles of Pleistocene Park, but removing trees and brush from all of Siberia (as well as Northern Europe, Alaska, Canada and Greenland) will require vast herds of the region’s former mega-herbivore: the woolly mammoth.  The Zimovs are showing that clearing woody vegetation exposes the soil to frigid winter air and allows clear fields of ice and snow to reflect sunlight. This keeps the ground frozen so it retains the greenhouse gases CO2 and methane that are currently being released by the thawing permafrost.

Eriona Hysolli collects a tissue specimen from a frozen mammoth trunk at the Mammoth Museum in Yukutsk, Siberia.

The American Chestnut Research & Restoration Project:

In May, Revive & Restore’s Board of Directors toured the laboratories and the field trial sites of the American Chestnut Research and Restoration Project. Researchers at the College of Environmental Science and Forestry (ESF) in Syracuse, New York discovered that resistance to a devastating fungal blight that could be engineered by inserting a single gene  from wheat (coding for oxalate oxidase) into the the genome of the American chestnut. Once the dominant tree in North America’s eastern hardwood forest, the tree was almost entirely wiped out by an non-native fungal blight introduced in the early 1900s. While not extinct, these trees only rarely reach maturity and the American chestnut will not survive indefinitely without intervention.

This is the most advanced of any genetic rescue project, making it a key model for Revive & Restore as our projects move beyond the planning and research phases and into the laboratory and implementation phases. After 30 years of research, the ESF research team led by Bill Powell is now seeking regulatory approval from several federal government agencies to plant the transgenic trees across its native range in North America. They are in the process of growing 10,000 blight-resistant American chestnut trees to jump start the restoration effort. If regulatory approval is granted, it would set a new precedent for restoring a native species in North America.

Ryan Phelan and Stewart Brand plant a blight-resistant American Chestnut in Syracuse, NY.

Suggested Reading

Popular Press

  • “Disease-Resistant Ferrets?” Powell Tribute – November 13, 2018. [Read here.]
  • “Meet the Scientists Bringing Extinct Species Back from the Dead,” Wall Street Journal –  October 9, 2018. [Read here.]
  • “Inside the Biomedical Revolution to Save Horseshoe Crabs and the Shorebirds That Need Them,” National Audubon Magazine – May 11, 2018. [Read here.]
  • “The Last Days of the Blue-Blood Harvest,” The Atlantic – May 9, 2018 [Read here.]

Revive & Restore Publications  

  • “De-Extinction,” Genes –  November 13, 2018. [Read here.]
  • “Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detection,” PLOS Biology – October 12, 2018. [Read here.]
  • “Experimental Investigation of the Dietary Ecology of the Extinct Passenger Pigeon, Ectopistes migratorius,” Frontiers in Ecology  and Evolution – March 5, 2018 [Read here.]
  • “Advancing a New Toolkit for Conservation: From Science to Policy,” CRISPR Journal – February 2018. [Read here.]