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Colossal Biosciences' Daring Ambition to De-extinct Dodo

Written by Ju Wan Shin '26

Edited by Jacqueline Cho '24

The mummified remains of the head of the Oxford Dodo - the only surviving soft tissue available for DNA research [1].


The dodo-goofy, stupid, clumsy. A fat and flightless creature who brought on its own demise with its million-year course of refusing to adapt and evolve. Yet the narrative falsely frames the poor dodo. Perfectly adapted for their natural habitat, the once thriving creature faced extinction with the arrival of Dutch colonists in Mauritius in the late 17th century, with their ruthless ways of hunting and killing, along with countless dogs, cats, and rats, their henchmen [2]. Now, a biotech startup Colossal Biosciences, backed with $225 million in investment, has added the dodo to their 'to-do-list' following the wooly mammoth and thylacines. It aims to de-extinct the long-extinct. Could this amend humanity's past sins?


Their grand plan started with 1.4 kilobases of the dodo's mitochondrial DNA. A team led by Beth Shapiro, a lead paleogeneticist and a scientific adviser at Colossal Biosciences, performed a Maximum Likelihood analysis of said DNA, pinpointing a monotypic Nicobar pigeon as the dodo's closest living relative [3]. Then, a complete genome of the dodo and the Nicobar pigeon was extracted from a bone powder of the "Gottorp" dodo Specimen and a pigeon tissue sample, respectively, using the Illumina sequencing method, a next-generation technology that can process millions of DNA segments in a single run [4]. Now, the only thing that stands in the way of a complete dodo revival: using genetic editing techniques such as CRISPR-Cas9 to edit the Nicobar pigeon's genome into a replication of that of a dodo.


However, with such a daring plan comes doubts; many criticize the shortcomings of the company's methods. First, DNA recovered from an ancient dodo sample, a bone powder in this case, due to heavy fragmentation, must be reconstructed through mapping against the de novo sequenced genome of the Nicobar pigeon. Because ancient DNA is typically very short due to post-mortem diagenesis, they map ambiguously, if at all, to the regions of DNA highly divergent from their reference, rendering them unrecoverable. Second, due to the limitations of current gene editing technologies, multiple rounds of edits are required to fully modify a genome since only a maximum of several tens to hundreds of edits can be introduced per cycle [5].


Now for the biggest criticism: conservation cloning for avian creatures is extremely difficult, if not impossible. An egg yolk is essentially a sea of nutrients with a minuscule white dot floating on top, the nucleus. For scientists, locating a tiny nucleus floating somewhere in the yolk is nothing short of a nightmare, let alone the fact that such a massive sample cannot be placed under a microscope to perform a nuclear transfer, so-called a "nucleus-swapping trick" that will fertilize an egg with a donor's genetic information. Avian embryos can't be placed in the surrogate mother's uterus either; they are dropped into an oviduct instead, where it tumbles down, adding layers of egg whites and shell membrane [6]. There is no uterus equivalent in avian creatures.


In response, Colossal Biosciences introduces an innovative approach of extracting avian primordial germ cells from bird eggs, which would then be genetically edited then inserted into embryos from a surrogate bird species. Resulting chimeric animals will produce dodo-like eggs and sperm, from which a dodo-resembling creature could be revived [7].


An extinct animal is brought back from the dead. Now what? Some point out that this industrially produced dodo will never be the dodo. Although genetically imprinted behavior patterns might be replicable, the social behavior of the animals, those inherited from one generation to the next, has forever disappeared with the last of the dodo [8]. The dodo proxy must also survive in the harsh 21st century, with new predators and ecosystems which in no way resemble that in the late 1600s. Securing a robust plan to ensure their well-being before their introduction to the new world will remain yet another challenge.


Vikash Tatapah, a conservation director at the Mauritian Wildlife Foundation, asks "if we could have such money, wouldn’t it be better spent on restoring habitat on Mauritius and preventing species from going extinct? [7]” After all, many experts agree that we are in the midst of a sixth mass extinction event, caused by our unsustainable use of land, water, and resources, and the inevitable climate change [9]. To many, it remains unclear whether such an expensive next-generation technology addresses the core reason why the dodo went extinct: the humans.


However, Colossal Biosciences responds that their goal is to create benefits far beyond single species. They point to their recent work on a vaccine for fatal elephant endotheliotropic herpes virus (EEHV) as one of many examples where the field of conservation could forever change by their efforts [2]. Even outside their daring ambition to revive the dodo, their passion for undoing the shameful human footsteps on nature, burns like a fire uncontainable.

 

References

[1] Museum of Natural History. The Oxford Dodo. [Internet]. 2020 [Cited 2023 Mar 6]. Available from: https://oumnh.ox.ac.uk/learn-the-oxford-dodo

[2] Reynolds M. Why Bother Bringing Back the Dodo? [Internet] [cited 2023 Mar 6]. Available from: https://www.wired.com/story/colossal-dodo-deextinction/

[3] Shapiro B, Sibthorpe D, Rambaut A, Austin J, Wragg GM, Bininda-Emonds ORP, et al. Flight of the Dodo. Science. 2002; 295, 1683.

[4] Soares AER, Novak BJ, Haile J, Heupink TH, Fjeldsa J, Gilbert MTP, et al. Complete mitochondrial genomes of living and extinct pigeons revise the timing of the columbiform radiation. BMC. 2016; 16, 230.

[5] Lin J, Duchene D, Caroe C, Zhang G, Gopalakrishnan S. Probing the genomic limits of de-extinction in the Christmas Island rat. Current Biology. 2022; 32, 1650 - 1656.

[6] Fritts R. The Surprising Reason Scientists Haven’t Been Able to Clone a Bird Yet. [Internet] [cited 2023 Mar 6]. Available from: https://www.audubon.org/news/the-surprising-reason-

scientists-havent-been-able-clone-bird-yet#:~:text=Birds%20have%20no%20such%20incubation,stick%20a%20bird%20clone%20embryo

[7] Callaway E. What it would take to bring back the dodo. Nature. 2023; 614, 402.

[8] Kenneally C. A ‘De-extinction’ Company Wants to Bring Back the Dodo. [Internet] [cited 2023 Mar 6]. Available from: https://www.scientificamerican.com/article/tech-company-invests

-150m-to-bring-back-the-dodo/#:~:text=In%20this%20sense%2C%20the%20word,when%20the%20dodo%20went%20extinct

[9] World Wildlife Fund. What is the sixth mass extinction and what can we do about it? [Internet]. 2023 [Cited 2023 Mar 6]. Available from: https://www.worldwildlife.org/stories/what-is-the

-sixth-mass-extinction-and-what-can-we-do-about-it#:~:text=The%20planet%20has%20experienced%20five,of%20a%20sixth%20mass%20extinction



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