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Colossal Biosciences

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Colossal Biosciences Inc.
Company typePrivate
IndustryBiotechnology
Founded2021; 3 years ago (2021)
Founders
Headquarters
Dallas, Texas
,
U.S.
Key people
Number of employees
85 (2023)[2]
Websitecolossal.com

Colossal Biosciences Inc. is an American biotechnology and genetic engineering company working to de-extinct the woolly mammoth, the Tasmanian tiger, the northern white rhinoceros, and the dodo.[1][3][4][5][6][7] In 2023, it stated that it wants to have woolly mammoth hybrid calves by 2028, and wants to reintroduce them to the Arctic tundra habitat.[8] Likewise, it launched the Tasmanian Thylacine Advisory Committee, a thylacine research project to release Tasmanian tiger joeys back to their original Tasmanian and broader Australian habitat after a period of observation in captivity.[9]

The company develops genetic engineering and reproductive technology for conservation biology. It was founded in 2021 by George Church and Ben Lamm,[3] and is based in Dallas, Texas.[10][11]

History

[edit]

Foundation

[edit]

In a 2008 interview with The New York Times, George Church first expressed his interest in engineering a hybrid Asian elephant-mammoth by sequencing the woolly mammoth genome.[4] In 2012, Church was part of a team that pioneered the CRISPR-Cas9 gene editing tool, through which the potential for altering genetic code to engineer the envisioned “mammophant" surfaced.[12] Church presented a talk at the National Geographic Society in 2013, where he mapped out the idea of Colossal.[3]

Church and his genetics team used CRISPR to copy mammoth genes into the genome of an Asian elephant in 2015.[13] That same year, Church's lab integrated mammoth genes into the DNA of elephant skin cells; the lab zeroed in on 60 genes that experiments hypothesized as being important to the distinctive traits of mammoths, such as a high-domed skull, ability to hold oxygen at low temperatures, and fatty tissue.[3][4] Church's lab reported in 2017 that it had successfully added 45 genes to the genome of an Asian elephant.[14]

In 2019, Ben Lamm, a serial entrepreneur, contacted Church to meet at his lab in Boston.[4] Lamm was intrigued by press reports of Church's de-extinction idea.[3]

Launch

[edit]

Colossal was officially launched on September 13, 2021.[3][4][15][16] The launch included a $15 million seed round led by Thomas Tull, Tim Draper, Tony Robbins, Winklevoss Capital Management, Breyer Capital and Richard Garriott.[17][12][18] In addition to the de-extinction of the woolly mammoth, Colossal, in partnership with Dr. Paul Ling of Baylor College of Medicine, hopes to synthesize the elephant endotheliotropic herpesvirus, a virus which infects and kills many young Asian elephants.[4][19]

Colossal also announced that the company's mission was to preserve endangered animals through gene-editing technology and use those same animals to reshape Arctic ecosystems to combat climate change.[20]

The company's genomic modeling software development could potentially bring forth advancements in disease treatment, multiplexed genetic engineering, synthetic biology, and biotechnology.[13][18] Colossal recruited mammoth and modern elephant experts Michael Hofreiter and Fritz Vollrath, as well as bioethicists R. Alta Charo and S. Matthew Liao for their consultation.[4] Other scientific advisory board members include: Carolyn Bertozzi, Austin Gallagher, Kenneth Lacovara, Beth Shapiro, Helen Hobbs, David Haussler, Elazar Edelman, Joseph DeSimone, Erez Lieberman Aiden, Christopher E. Mason, and Doris Taylor.[8][21][22][23][24]

In October 2021, Colossal announced its partnership with VGP; through this collaboration, Colossal will provide funding for VGP to sequence and assemble Asian, African bush, and African forest elephant genomes for preservation purposes. These genomes were made publicly accessible for research without use restrictions in July 2022 and May 2023, respectively.[25][26][27]

In March 2022, Colossal raised $60 million in a Series A funding round led by Thomas Tull with participation from Animoca Brands, Paris Hilton, Charles Hoskinson, bringing the total funding to $75 million.[28][29]

Colossal spun out its software platform, Form Bio, in September 2022 with $30 million in funding. Lamm has stated that Colossal is run like a software company, and monetization will stem from technologies developed by the company. Form Bio has developed an AI-based software platform designed to help scientists manage large and complicated datasets.[8][30]

In January 2023, Colossal completed a Series B funding round, raising an additional $150 million and putting the company's valuation at over $1 billion.[24] The same month, Colossal launched its Conservation Advisory Board, which includes Forrest Galante, Iain Douglas-Hamilton, Mead Treadwell, and Aurelia Skipwith as its members.[8][24]

In October 2024, Colossal announced $50 million in funding for its launch of the Colossal Foundation.[31]

Science and development

[edit]

Because the woolly mammoth and Asian elephant share 99.6% of the same DNA, Colossal aims to develop a proxy species by swapping enough key mammoth genes into the Asian elephant genome.[4] Key mammoth genealogical traits include: a 10-centimeter layer of insulating fat, five different types of shaggy hair, and smaller ears to help the hybrid tolerate cold weather.[32]

Colossal's lab will pair CRISPR/Cas9 with other DNA-editing enzymes, such as integrases, recombinases, and deaminases, to splice woolly mammoth genes into the Asian elephant.[20] The company plans on sequencing both elephant and mammoth samples in order to identify key genes in both species to promote population diversification. By doing so, Colossal hopes to prevent any rogue mutations within the hybrid herd.[20] Colossal set a goal for the company to grow a woolly mammoth calf by 2028.[33]

The company plans to use African and Asian elephants as potential surrogates and largely plans to develop artificial elephant wombs lined with uterine tissue as a parallel path to gestation.[3][4][34] Colossal scientists plan on creating these embryos by taking skin cells from Asian elephants and reprogramming them into induced pluripotent stem cells which carry mammoth DNA.[4][35] Lamm stated that Colossal will use both induced pluripotent stem cells (iPSC) as well as somatic cell nuclear transfer in the process.[13]

In July 2022, VGP and Colossal announced that they successfully sequenced the entire Asian elephant genome; this is the first time that mammalian genetic code has been fully sequenced to this degree since the Human Genome Project was completed in the early 2000s.[26]

In August 2022, Colossal announced that they would launch a thylacine research project, in hopes of "de-extincting" the Tasmanian tiger.[36] Colossal plans to reintroduce the thylacine proxy to selected areas in Tasmania and broader Australia and claims that, by doing so, this will re-balance ecosystems that have suffered biodiversity loss and degradation since the species disappeared.[37][38] A successful thylacine proxy birth could also introduce new marsupial-assisted reproductive technology which can aid in other marsupial conservation efforts.[39] Colossal is partnering with the University of Melbourne, and the project is led by Andrew Pask.[37][38] The Tasmanian Thylacine Advisory Committee was launched in December 2023.[9]

In January 2023, Colossal announced the formation of its Avian Genomics Group, which will be dedicated to reconstructing the DNA of the dodo bird, which went extinct in the 1600s.[40] Led by Beth Shapiro, who serves as Chief Science Officer to Colossal,[31] this research group aims to create a hybrid composed of specific traits most commonly associated with the dodo and plans to reintroduce these hybrids into their respective environments. Colossal will be working with primordial germ cells to pair dodo DNA with the genome of the Nicobar pigeon, the extinct dodo's closest living relative.[7][41]

Breaking, a plastic degradation and synthetic biology startup, was launched in April 2024. Gestated at Colossal, Breaking discovered X-32, a microbe that is capable of breaking down various plastics in as little as 22 months while leaving behind carbon dioxide, water and biomass.[42]

It was reported in 2024 that Colossal successfully produced the first-ever elephant and dunnart iPSCs.[43]

In October 2024, the company announced that it had rebuilt a 99.9% accurate genome of the thylacine, using a “pickled” 110-year-old fossilized Tasmanian tiger skull. This marks “the most complete ancient genome of any species known to date” and provides a full DNA blueprint to potentially bring back the Tasmanian tiger.[44][45]

Future de-extinction projects

[edit]

Outside of their first four projects, Colossal Biosciences has stated that they have a "long list" of species that they want to revive and reintroduce to appropriate ecosystems. Such species include Castoroides, Arctodus, and Steller's sea cow.[46] Ben Lamm has stated that he and his company want to revive Steller's sea in cow once they have developed an artificial animal womb, as there are no adequate living relatives of the extinct sea cow to act a surrogate species.[47] Colossal has also done genetic research for species such as the Irish elk, great auk, bluebuck, ground sloth, moas, and woolly rhinoceros with the intent to potentially revive them in the future.[48]

Conservation

[edit]

In October 2022, Colossal announced that it was developing a vaccine for elephant endotheliotropic herpesvirus (EEHV), in partnership with the Baylor College of Medicine.[49]

In May 2023, Colossal partnered with the Vertebrate Genomes Project to successfully generate the first high-quality reference genome of an African elephant. This sequencing work is part of a long-term conservation effort for the endangered elephant species.[50]

In September 2023, Colossal partnered with BioRescue to help save the northern white rhino from extinction by using reproduction technology and stem cell technology, as the subspecies is functionally extinct with only two known infertile female members left.[51]

Colossal and Zoos Victoria began a conservation project in October 2023 to preserve the Victorian Grassland Earless Dragon as well as sequence its genome.[52][53]

In November 2023, Colossal announced a research partnership with Save the Elephants to track African elephants in the Samburu National Reserve. Save the Elephants has already tracked over 900 elephants in the area, using drones equipped with high-resolution infrared cameras. Colossal plans to use pose estimation to develop algorithms for labeling elephants and automatically identifying individual & collective social behavior.[54][55]

Colossal also began a partnership with the Mauritian Wildlife Foundation in November 2023. Under this collaboration, the organizations will work to restore “critical ecosystems through invasive species removal, revegetation, and community awareness efforts.”[56] Additionally, Colossal will also focus on the rewilding of the dodo bird as well as the genetic rescue of the pink pigeon.[57]

In March 2024, Colossal and Re:wild partnered together to establish a “10-year conservation strategy” to accelerate efforts to “save species on the brink of extinction, search for lost species, and restore key habitats for species recovery and rewilding.”[58]

In May 2024, Colossal and the University of Melbourne announced the successful engineering of cane toad toxin resistance in marsupial cells, as part of conservation efforts for the northern quoll.[59][60] Colossal’s refined engineering resistance strategy can create over 6,000-fold increased resistance with just one edit to the genome.

The first-ever mRNA vaccine for elephant endotheliotropic herpesvirus (EEHV), developed by Colossal, the Houston Zoo, and the Baylor College of Medicine, was administered to an elephant in July 2024.[61]

In October 2024, Colossal announced its launch of the Colossal Foundation, a non-profit initiative that utilizes Colossal-developed science and technology methods for partner-led conservative efforts. Included in its conservation agenda is the Colossal Biovault, "the world's largest distributed biobanking initiative." The Colossal Biovault collects tissue samples of endangered species in hopes to allow cell lines to become accessible and stored in domestic partner facilities. Its first projects include: Sumatran rhinoceros, vaquita, and ivory-billed woodpecker.[31]

Reception

[edit]

In 2022, Colossal was listed as one of the World Economic Forum's Technology Pioneers and was named Genomics Innovation of the Year by the BioTech Breakthrough Awards.[62][63]

Colossal was included as part of Time's 100 Most Influential Companies 2023 list.[10]

Colossal has received significant backlash for its explanation to why dinosaur de-extinction is impossible, or at least not possible in the way it is depicted in science-fiction, mainly from fans of the Jurassic Park media franchise. The CSO, Beth Shapiro even became the target of an online harassment and trolling campaign from Jurassic Park fans.[64][65]

References

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  2. ^ Thompson, Paul (January 31, 2023). "Colossal Biosciences raises $150M, plans to bring back dodo". Austin Business Journal. Archived from the original on January 31, 2023.
  3. ^ a b c d e f g Zimmer, Carl (2021-09-13). "A New Company With a Wild Mission: Bring Back the Woolly Mammoth". The New York Times. Retrieved 2021-10-26.
  4. ^ a b c d e f g h i j Michael Greshko (September 13, 2021). "Mammoth-elephant hybrids could be created within the decade. Should they be?". National Geographic. Archived from the original on September 13, 2021.
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  26. ^ a b "Colossal Biosciences and the Vertebrate Genomes Project Sequence the Asian Elephant Genome, Chromosome to Chromosome". BioSpace. July 12, 2022.
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  42. ^ "Greentech Company Breaking Launches From Colossal Biosciences". Built in Boston. April 17, 2024.
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  44. ^ Vishwam Sankaran (October 17, 2024). "Scientists say 'pickled' fossil could help bring back extinct Australian marsupial". Independent.
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  46. ^ "First it was the dodo – now scientists want to resurrect the giant bear and jumbo beaver". The Telegraph. 2024-10-05. ISSN 0307-1235. Retrieved 2024-11-27.
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  48. ^ "Our Species". Colossal. 2023-01-31. Retrieved 2024-11-27.
  49. ^ "Saving Baby Elephants from a Deadly Herpes Virus". Discovery. October 5, 2022.
  50. ^ Alexandra Skores (May 18, 2023). "Colossal Biosciences says it's one step closer to bringing back extinct species". The Dallas Morning News.
  51. ^ "Colossal Biosciences Joins BioRescue in Its Mission to Save the Northern White Rhino From Extinction". BioSpace. Retrieved 2024-02-07.
  52. ^ David Seeley (October 25, 2023). "Here Be Dragons: Colossal Partners with Zoos Victoria To Save Reptile Once Thought Extinct". Dallas Innovates.
  53. ^ Adam Morton (October 24, 2023). "Imagine more dragons: US biotech firm aims to breed tiny Australian lizard that is near extinction". Guardian.
  54. ^ Lance Murray (November 9, 2023). "Colossal and Save the Elephants Use Drones and Machine Learning To Track African Elephants". Dallas Innovates.
  55. ^ Alison Snyder (November 9, 2023). "AI and drones are helping scientists study secrets of elephant behavior". Axios.
  56. ^ David Seeley (November 27, 2023). "Colossal Partners with Mauritian Wildlife Foundation To 'Rewild' the Dodo, as Another Bird Gets a 'Genetic Rescue'". Dallas Innovates.
  57. ^ Irving Mejia-Hilario (November 22, 2023). "Colossal Biosciences finds a home for one extinct species". Phys.
  58. ^ David Seeley (March 29, 2024). "The Last Word: Re:wild's Barney Long on Partnering with Dallas-Based Colossal To Save Species Facing Extinction". Dallas Innovates.
  59. ^ James Fair (May 9, 2024). "A rare Australian marsupial is being genetically modified to save it from extinction. Here's how". Discover Wildlife.
  60. ^ "Gene editing could make quolls resistant to cane toad toxin". Lab Online. May 14, 2024.
  61. ^ Patrick Greenfield (July 15, 2024). "First Asian elephant vaccinated in fight against deadly herpes virus". Guardian.
  62. ^ "Technology Pioneers 2022". World Economic Forum.
  63. ^ "2022 Winners". BioTech Breakthrough Awards.
  64. ^ Shuyi, Lee (2024-09-11). "Dinosaurs' return deemed impossible by scientist". Thaiger World. Retrieved 2024-09-16.
  65. ^ Me, the social media manager, when people get mad at Dr. Beth Shapiro in the comments. Retrieved 2024-11-27 – via www.youtube.com.
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