Ted and Julie McMasters both came from big families, so as soon as they were married they knew they wanted to have kids. Unfortunately, Julie kept having miscarriages which prevented them from having the large family they always wanted. Finally, she was able to have their son Jason. When Jason was two years old, Julie was pregnant again, which was a miracle after all the miscarriages.
Jason and Julie then got into a terrible accident resulting in Julie’s miscarriage and Jason’s death. On top of all this, Ted is sterile due to testicular cancer. So, even though there was no damage to his wife’s uterus, they were unable to have more children. A doctor approached the couple, suggesting they contact the director of a human cloning company who could potentially clone Jason so they could have him back. Being asked to clone your dead son is not a simple question though and there are many factors to consider before making the decision.First of all, how is it even possible to clone a human being? Reproductive cloning is not an easy process.
One method is somatic cell nuclear transfer or SCNT, it involves using somatic cells which are cells in the body other than egg and sperm cells. The process involves removing the nucleus from an egg and replacing it with the nucleus from the somatic cell of the organism being cloned. This now “fertilized egg” or embryo can be placed in a surrogate mother and should ideally develop normally. In SCNT, you can implant any somatic cell’s nucleus into the egg, including stem cells or differentiated cells. However, obviously, this artificial fertilization through SCNT is very different than normal fertilization. This can be due to a number of things including differences in chromatin state.Chromatin in a cell is located in the nucleus and contains the DNA or genetic material of the cell. Chromatin is more than just DNA though, it contains proteins called histones that have positively charged tails that are attracted to the negative backbone of DNA and wrap around it.
These histones limit access to DNA. The chromatin in egg and sperm cells, known as germline cells, is very different than the chromatin in somatic cells. Epigenetic tags, also known as chromatin modifications are common on somatic cells and can change the chromatin structure and thus the ability of RNA polymerase to bind to the DNA in order to transcribe it, controlling gene expression. Chromatin modifications include acetylation, methylation, and phosphorylation. These chromatin modifications are all histone modifications, though methylation can occur on histones or on the DNA itself. Acetylation neutralizes the positive charge of the histone tail and causes the tail to be not as attracted to the negative backbone of DNA, which in turn loosens the chromatin, leaving it more open for transcription.
Phosphorylation leaves the histone tail with a net negative charge which will also cause the tail to be less attracted to the negative backbone of DNA and loosen the chromatin for easier access. Histone methylation, on the other hand, can tighten or loosen chromatin depending on the environment and the methyl group that is being added to the histone tail. DNA methylation, however, makes the DNA tighter and gets in the way of transcription. Although sperm and egg cells still have some chromatin modifications many are removed during formation of a zygote, there are probably more modifications on somatic cells, whose chromatin is constantly being manipulated. When a somatic cell with modified chromatin is put in an egg, the egg will try to reset the epigenetic tags to look like a normal germline cell but this is not always possible and does not always happen correctly.
Imprinting, where certain genes from the maternal and paternal parents are turned on or off is required for normal development. These imprinted genes keep their epigenetic tags even when the embryo develops. However, the epigenetic tags in place in an embryonic cell formed from normal fertilization are probably very different from the epigenetic tags in place in a somatic cell from an organism that has been alive for some time. Therefore, if you were to use a somatic cell from two-year-old Jason in the process, it would be very different than a cell from embryonic Jason and it is very likely that the clone would not be exactly like Jason. Epigenetic tags are a possible explanation for why cloning is so inefficient. For example, it took scientists from the Roslin Institute 277 tries to clone one living, breathing sheep (Cloning Dolly the sheep).
Trying to clone Jason could be a very long process and require many tries before Ted and Julie can get another son. Although the egg may try to alter the chromatin by removing its epigenetic tags to promote normal development, it isn’t always possible. Human cloning is also very different than cloning an animal this is because cloning a primate is different than cloning other mammals. This is in part because of spindle fiber formation when embryonic cells try to divide. When the nucleus is removed from the egg in one of the first steps of SCNT in primates, some proteins needed for correct spindle function are removed.Epigenetic tags on somatic cells and improper cell division due to faulty spindle fibers are factors that could contribute to an embryo’s failure to develop correctly. And even if the embryo is able to develop correctly, the organism could still have physiological issues due to the differences in chromatin state because chromatin in a mature somatic cell is very different than chromatin in a germline cell. These physiological issues could result in a lower quality of life or even a shorter lifespan.
There is a high chance that cloning Jason would take many tries and even if it was done successfully his clone could have many issues. Relative cell age could also cause difficulties in cloning Jason. As chromosomes replicate and divide their telomeres which are just the ends of the chromosomes shorten each time. They continuously shorten until eventually the chromosome is too short to divide anymore and the cell dies. Germline cells, however, have telomerase, an enzyme that can stop the shortening by adding nucleotides to the ends of the chromosomes. If a somatic cell that has shortened chromosomes is used in SCNT to create a clone then this cell would be very different than how a normal germ line cell would be and would likely result in a different looking clone or a clone with physiological issues.
This is because genes could be missing or not expressed when the chromosomes are shorter. A study done by Atsuo Ogura in which mice were cloned provides some evidence that cloned animals don’t have as long of a lifespan as animals that are produced through normal reproduction (Ogura et al). This is likely because of issues they have with complications due to differences in chromatin state and improper cell division from faulty spindle fibers (Cohen).Not even considering the ethics surrounding the issue of cloning your dead child, it has become clear that Ted and Julie should just accept the death of their son and look into having a son another way, through either a sperm donation or adoption. Cloning using SCNT is very different than normal reproduction through fertilization. Differences in the chromatin state because of epigenetic tags and chromatin modifications or the relative age of the cell and length of the chromosomes as well as difficulties in cell division because of faulty spindle fibers make it likely that the clone will have physiological issues that could lead to a lower quality of life and a shorter lifespan. This cloning is also a very inefficient process that could take a toll on Ted and Julie. In my opinion, it is best if Ted and Julie seriously consider other options for having another child.
