Transforming Tasmanian Devils: Potential Uses for Synthetic Biology in Conservation

Can we use biotechnology to save Tasmanian devils from extinction? [image source]

Last post, I talked about the facial cancer that’s wiping our Tasmanian devils. We understand the problem fairly well – the facial cancer spreads unchecked among the devil population because devils have very similar MHCs, the cellular “flags” that allow your immune system to tell whether a cell is your own or a foreign invader. When the devils fight, cancer cells can get transferred from an infected devil to the face of an uninfected devil. Because of their similar MHCs, the immune system doesn’t recognize the invader and the cancer easily takes root. Since MHC similarity is the root of the problem, introducing MHC diversity might be the solution. What if scientists could create Tasmanian devils with different MHC complexes and introduce them back into the population? These different devils would be immune to the face cancer. In addition, devils born from a match between a Devil 2.0 and an original model would have a mix of their parent’s MHC complexes, creating even more variation. This is all assuming we could make a Tasmanian devil with new MHCs in the first place, something we may be able to do in the near future thanks to advances in genetic engineering and “cloning” technology.

 

Adding MHC Varaiation to the DNA

The first step is to code new MHC sequences into the devil genome. You could design new devil MHC sequences, or search for DNA samples from devils with different or less common MHC groups. Once you have these sequences, you have to insert them into the right place. Early genetic engineering suffered from the problem of poorly targeted gene insertion. Using viruses, scientists could handily integrate new genes into the genome; however, if the insertion site of these genes isn’t tightly controlled, they can disrupt essential native genes or turn on nearby a cancer-causing genes (aka oncogenes). In a gene therapy trial to treat severe combined immunodeficiency, gene insertion near an oncogene led to leukemia in some of the trial participants.

Viral gene therapy hijacks the ability of viruses to insert their genes into the genomes of their infected host. Scientists replace the viruses genes with the ones they want to insert instead [image source]

Genetic engineering today is a different story. Scientists have gotten very good at inserting DNA at specific locations in the genome. They use special proteins (or sometimes even RNA) that can target specific sequences in the genome, and then insert the new DNA between those sequences. Recently, these new genetic engineering techniques made headlines when scientists used them to create immune cells (T-cells) that can take out leukemia cancer cells. The therapy is currently in clinical trials. This same technology could be used to add new MHC sequences to a Tasmanian devil genome.

From new devil genome to new devil pups

Okay, so now we have a collection of altered devil cells. How do we turn these cells into an actual Tasmanian devil? The classic technique to turn an isolated cell into a whole organism is somatic cell nuclear transfer (SCNT), the cloning technique that was used to create Dolly the sheep. SCNT combines two cells by replacing the nucleus of a fertilized donor egg with the nucleus of a cell from the animal you want to clone. The word somatic refers to the fact that the non-egg nucleus comes from a non-reproductive body cell (e.g. skin, liver, fat), which are called somatic cells.   

The nucleus contains the genetic blueprints that tell the egg what animal it should become, and the cytoplasm of the egg (everything outside the nucleus) contains the cellular construction workers and machinery who will translate those blueprints into an animal. By taking out the donor egg nucleus and putting in a new one, you are swapping the egg blueprints for the blueprints of whatever your new nucleus came from. After implanting this altered egg in a surrogate mother, (if nothing goes wrong during gestation) you’ll get a new baby based off the inserted nucleus.

A schematic of SCNT, as used to create Dolly the sheep. [image source]

However, there are significant problems with SCNT. DNA is packaged differently in body cells compared to egg and sperm cells – it’s modified to make sure only the genes that relate to that cell’s function are activated. These modifications are what make a skin cell a skin cell and not a liver cell. In addition, DNA ages as you do. Mutations build up and protective “caps” on the end of the DNA molecule wear down with every cell replication. These modifications can cause improper fetal development or health problems later on.

One way to get around the problems of SCNT may be to create egg and sperm cells from body cells. Cells inside early embryos are blank slates, and can become any of the specialized cells in your body (e.g. bone, skin, and pancreas). Using genetic engineering, scientists can take these specialized cells and turn them back into embryonic-like blank slates called induced pluripotent stem cells (iPSCs). IPSCs can be theoretically reporgrammed into any specialized cell cell in the body – neurons, pancreatic beta cells, and white blood cells have all been produced from iPSCs in the lab.

To create iPSCs, scientist expose normal body cells to special factors that turn the body cells into blank-slate embryonic-like cells. These iPSCs can then be differentiated into your specialized cell of choice. [image source]

More importantly to reproductive biology, viable sperm and egg cells have already been made from mouse iPSCs. Fertilized eggs made with these lab-generated sperm or egg cells successfully became healthy baby mice. Although iPSC techniques are still in their nascent stages, it’s very possible that they could one day be used to turn MHC-altered Tasmanian devil cells into Tasmanian devil pups.

De-extinction and pre-extinction

The focus at TEDx DeExtinction was on how these technologies could be used to bring back extinct species. For example, Dr. Alberto Fernández-Arias semi-successfully used SCNT to create a baby Pyrinian Ibex: the ibex made it through pregnancy fine, but died several minutes after birth due to a lung defect.  Synthetic biology techniques have great potential for conservation (or “pre-extinction”) efforts as well. Before their population was culled by face cancer, Tasmanian devils were in no danger of extinction. If scientists could create a more varied devil population that wasn’t susceptible to the cancer, the devils could likely thrive again. However, careful breeding and monitoring would have to be used to prevent another genetic bottleneck. You don’t want to replace the original devil population with a similarly stunted genetic sampling. Synthetic biologists and conservationists would have to work together to create a varied and resilient devil population.

De-extinction and pre-extinction scientists could cooperate to create an overall healthier Tasmanian ecosystem, one that might prevent future facial cancer outbreaks among the devils. Dr. Michael Archer, who is trying to bring back the thylacine (or “Tasmanian tiger”) recently, discussed this possibility on NPR’s Science Friday. Archer talked about how losing the thylacine disrupted the ecosystem balance and allowed the devils to overpopulate:

“If we could get the Thylacine back, put that king of beasts back in the throne, which is still warm and waiting, it would suppress the number of devils, keep them at a manageable level and the disease would burn itself out wherever it started. So getting these ecosystems back by putting in key species can be critical to maintaining the stability of them.”

Even if the thylacine never returns, de-extinction advances could be used to keep Tasmanain devils from a similar fate. The World Wildlife Federation estimates that over 10,000 species go extinct every year, and many of these extinctions are caused by humans. In the wake of this devastation, we must save every species we can, and de-extinction driven synthetic biology can give us new means to preserve species like the devils.

After all, who would want to lose a face like this one?

Image credit: Wayne McLean ( jgritz), via Wikimedia Commons