SynBio10: SynBio and de-extinction (v1.0)

Given our growing ability to build organisms using genetic blueprints, is true extinction a thing of the past? Probably not. On the other hand, Synthetic Biology is being used in research to create hybrid versions of the wooly mammoth, passenger pigeon, American chestnut and other extinct species. 

No one really knows how many species really exist or existed, but it is estimated that up to 90% of all species are yet to be discovered. Many species that are quietly going extinct are plants, insects, marine life and microorganisms, often tied to humanities activities. These species play a large role in supporting the larger animal species we more focus on. Many believe we are in the middle of a sixth mass extinction wave in earth's history. Synthetic Biology ushers in new tools to help with de-extinction although some people do have reservations about such attempts. The new tools are available but synthetic biology is NOT the solution to the bigger extinction problem. 

Scientists are now able to synthesize extinct and extant DNA and put it in host cells to be implanted as surrogate embryos. Back in 2013, George Church made international news with a report that he was trying to de-extinction Neanderthals. However, what he had really said was just how the feat might be technically possible given the viable Neanderthal DNA recently discovered and sequenced. In 2021, the journal Cell published a report that a monkey human Chimera had been produced where human stem cells were injected into monkey embryos and cultured for 20 days. The goal was not to create cross-species mutants with specific physical features like something out of an X-Men comic; rather, the researchers sought to unravel the mysteries of early human development. 

There are many technical barriers today to de-extinction a species as complex as a Woolly Mammoth. But let us step through it as an example. The first challenge is obtaining a suitable sample to determine the full genetic sequence. Another challenge is this sample could be adulterated with genes of microbes or other life. However, these problems have been overcome and the mammoth genome has been sequenced. Next finding viable cells to be cloned can also be challenging. The old cells in the samples are no longer viable. The only option is to create new cells to insert synthesized mammoth DNA into. Currently this is not feasible. We can get close by using cells from Asian elephants its closest relative. So here are the steps. 

1. Genome of mammoth sequenced. Synthesized.  
2. DNA is spliced with skin cells from Asian elephants. 
3. Skin cells reprogrammed to become stem cells and added to egg from Asian elephant. 
4. Eggs stimulated to turn into embryos. 
5. Embryos placed in a surrogate and ultimately into an artificial womb. 
6. The result is a fusion of Asian Elephant and Mammoth. 

But a mammoth's gestation is like an elephant - about 2 years, and mammoths are big so it would be quite a feat for an Asian elephant surrogate to pull off!! Ouch!! The process also involves extracting good eggs from an Asian elephant which is another technical hurdle but possible. Lastly an artificial womb that can accommodate a mammoth has never been created!

In 2021 Dr Jacob Hanna and colleagues published in nature that they had removed mice from gastrulation 5 days after conception and placed them in an artificial womb and made a premature delivery. This work has implications for de-extinction efforts.

SIDE NOTE: Dr Jacob Hanna, a Palestinian Arab-Israeli who is an expert in embryonic stem cell research, is well known for first developing a technique for extended culturing of mouse embryos outside the uterus (ex utero) in 2021, capturing development from before gastrulation until late organogenesis outside the uterus, subsequently applying his technique for making the first synthetic complete embryo models of mice in 2022, and then of human in 2023 that can be made solely from embryonic pluripotent stem cells and outside the womb. 

In summary de-extinction is possible but challenging, and its benefits needs to be carefully weighed before embarking on a specific project. SynBio can be used to stave off extinction for an ecologically important species or resurrect an important extinct species. But this technique can practically be only used for a few species and does little to dent the scale of extinctions currently taking place.