Germ Line Therapy

Katherine Circle

Copyright 1998

When I was a student in elementary school I was first told about genetics. I was told that traits are passed from parents to offspring and that each parent contributes equally. Someday, I was told, parents will be able to go down to the corner drug store and pick out what kind of baby they want. They could pick things like blue eyes, high intelligence and could even pick out the sex of their child. At the time I was being told this I believed that I would see it in my lifetime. I expected that by the time I was having children I would be able to pick their traits. I was especially excited to think that my children would not inherit my genetic disease. I wasn’t quite sure how all of this would work, but I was curious to find out. As I progressed in my scholastic career I went on to learn more about genetics. I finally decided that genetics was the field of study that I wished to pursue in college. Once in college I learned that determining your child’s traits was not as easy as going down to the corner drug store and taking a pill, as I had imagined when I was a child. In fact determining most traits, such as eye and hair color was probably not even in the foreseeable future. What was involved I couldn’t even begin to understand as a freshman in college. The more I understood about molecular biology, the less feasible trait determination seemed. Then along came Dolly, the cloned sheep.

For some time scientists have been pursuing the idea of germ line therapy. Germ line therapy is essentially alterations made to the germ cells. Germ cells are eggs, sperm and early embryos (Henzig 1998). Any manipulation to the germ line would be transferred to future generations. Any corrections made at this stage would not need to be made again in that person’s descendants. Traditional gene therapy on adult subjects is called somatic cell therapy. This type of gene therapy must be repeated for each affected person in succeeding generations (Svitil 1998). Dolly was an important discovery because she was the first animal to be created from an adult differentiated cell. This cloning technique made germ line research much easier. Adult cells are more abundant than embryonic cells, and there should be no objection to doing research on differentiated cells from an adult donor. This new technique also opened up a new line of genetic therapy. Now we can explore the processes of development and learn how to create genetic cures for ourselves using our own cells. We can take our own differentiated cells and cause them to undifferentiate. We can then fix the problem in our organ or other body structure and replace the defective one. Differentiated cells are cells that have already become what they are supposed to be, such as muscle or bone or brain cells. Plants are known to be totipotent, that is one cell from a plant can grow into an entirely new organism. This is a type of natural cloning. Some reptiles and amphibians are pluripotent. They can regenerate lost body parts from adult differentiated cells by regressing the necessary cells to an earlier undifferentiated state, but they cannot form an entirely new organism. No mammal has ever been known to have this ability in nature.

The secret to Dolly seemed to be in the quiecing of the cells. A quiescent cell is frozen into a phase of the cell division that causes the chromosomes to be susceptible to reprogramming of the developmental mechanisms. The cells undergo a chromosomal reconfiguration, which is then completed by fusing the cell to a new enucleated egg. The fusion with the egg created an embryo with a complete genetic complement similar to that of a normally fertilized egg (Beardsley 1997).

Before Dolly, researchers were able to fuse undifferentiated embryonic cells to an enucleate egg and achieve offspring. These offspring would then be clones of the donor embryo or, if more than one individual was made from the same embryo, clones of each other. By using an adult differentiated cell some important discoveries were made about cell development. Before Dolly it was not known if the DNA in adult cells was turned off when not needed or if it was permanently altered. Dolly proves that unneeded DNA is stored and can be used if needed (Register Wire Services 1997). The most important implication of this is that someday we may be able to regenerate a diseased organ with the proper functional inserts and not need to worry about tissue rejection.

Another important step to this end came when researchers at Johns Hopkins University were able to cultivate human stem cells. These are undifferentiated embryonic cells or cells that do not yet have a determined fate. Theoretically stem cells could become any type of tissue that is needed if given the proper signals to become that tissue. An enucleated stem cell could in theory receive a cell nucleus from the adult in need of the transplant. This would essentially eliminate tissue rejection because the tissue would have exactly the same DNA as the host organism (Johns Hopkins Medical Institutions 1998).

A scientist at Advanced Cell Technologies came up with an alternative to using human fetuses. He fused one of his own adult cells to an enucleated cow egg (Powell 1998). Proteins in the cow egg are able to "reset" the human DNA, which causes the cell to become an embryonic human stem cell. At this point it is not known how long the hybrid cells could live. In other experiments a cow egg was fused to the adult cells of another livestock animal, it was then implanted into a cow surrogate mother. The embryos seem to have implanted in the host uterus, but only survived for about seven days. The most important thing learned from this experiment is that embryonic development employs similar mechanisms in a wide variety of mammals. This is important for human developmental studies because we now know that what does or doesn’t work in a cow will be the same for humans. Developmental experiments can be carried out on other animals and the knowledge can be extrapolated to humans.

Ethicists are concerned because human embryos are normally used to obtain human stem cells. It is possible for a single stem cell to become an entire organism, so in essence scientists are keeping people in petri dishes and not allowing them to mature past the blastula stage. Ethicists are also concerned about a hybrid between a human and a cow. What is especially troubling is that this cell can grow into a complete person. This person would then contain bovine DNA. The benefits of germ line therapy seem limitless. Every year many genes that lead to medical disorders are discovered. In 1997 genes were discovered for epilepsy, mental retardation, Parkinson’s disease, breast cancer, heroin addiction, glaucoma and obsessive-compulsive disorder to name just a few (Glausiusz 1997). Germ line therapy may be able to help cure these diseases in the present population and eradicate it from future generations. Adult body cells are much more abundant than embryonic cells, and no fetuses are sacrificed to make new tissue. Only the original colonies of stem cells, which are already in existence, need to be used for future organ cloning techniques.

Germ line therapy is also simpler that somatic cell therapy. It is already a well-established procedure in animals that has been used since the early 1980s (Register Wire Services 1997). Cloning is more accurate in an embryo than microinjection. In microinjection, naked DNA is injected into the nucleus of a fertilized egg. Only a small portion of the cells actually incorporate the desired DNA. With cloning, scientists will know before implantation if an embryo has the desired trait (Svitil 3/2/98). The downside of this type of therapy is that it is very new in humans and has yet to be perfected. One ethical concern is the vectors used to transfer the DNA. The vector DNA would also incorporate into the cell DNA and become a part of the host DNA in all cells in the body. Some see this as resulting in "humans that are not fully human-who have alien characteristics of viruses and other species" (Natural Law Party 1998). Even the artificial chromosomes that are now being used are often made from yeast, which is again alien DNA.

Other concerns are that somatic cell therapy has never produced a clinical success. Harmful mutations may occur and be passed on to future generations. Proteins may serve several functions that we are unaware of that may lead to complications if we change them. Unanticipated interactions with wild type alleles may occur. The greatest concern is that this type of therapy may interfere with evolution (Natural Law Party 1998). Changing ourselves may create descendants so different from us that "they do not even recognize us as fully human" (Wertz 1998). One major concern is that our society will not be satisfied with merely curing disease. A treatment often starts out as therapeutic, but quickly moves on to enhancing. Plastic surgery, breast implants, and growth hormone therapy are all examples of this trend (Henig 1998).

Ethicists are often concerned with the "slippery slope". Once you start down a certain path it is hard to stop. Bioethicist Eric Juengst says, "There is no slippery slope to genetic enhancement. As soon as we approve [a treatment] we’re already at the bottom." On the other hand, W. French Anderson of the University of California, who first used somatic cell therapy in 1990 said, "In principle, I’m all for it on the most fundamental of grounds: human nature. None of us want to pass on to our children lethal genes if we can prevent it" (Henig).

Personally, I agree with James Watson who asked, "If we can make better human beings by knowing how to add gene, why shouldn’t we do it? The biggest ethical problem we have is not using knowledge." (Henig) I also agree that genetic alterations will eventually be used for enhancement procedures. I think that the world will be much worse off if parents are allowed to choose their child’s traits. Parents really do have their hearts in the right places, but they are looking out for their own child’s best interest. No parent is going to want to choose a child that will perform well only in the unskilled labor job market. Every parent will want a smart child that will excel at science and math. There are not many jobs out there in these types of fields, and with everyone being super smart competition will be tougher. A world full of only intelligent people may seem like a utopia to some of us, but in the end it surely won’t be. Even in a world of the super smart, someone will need to do the jobs that no one else would want. The day to day running of the world does require intelligence, but the super intelligent would not be interested in that type of job. In essence, in a world full of Einsteins, who will work at McDonald’s? Another important factor to consider is that most parents want boys. With only boys being born, who will be able to create the next generation? Similar things have happened in third world countries where infanticide is commonplace. With all of our super smart men I’m sure something could be figured out, but then our society begins to look like Brave New World and no one wants to live like that. I do think that there can be a happy middle ground. If people with calmer heads prevail we will be able to cure disease using germ line therapy without going totally overboard and destroying ourselves in the process.


Beardsley, T. (1997) A Clone in Sheep’s Clothing. Obtained from:

Glausiusz, J (1997) The Year in Science Genetics. Obtained from:

Henzig, R. (1998) Tempting Fates. Discover 19(5) 58-66

Johns Hopkins Medical Institutions (November 5, 1998) Hopkins Research Team. Cultures Long-Awaited Human Embryonic Stem Cells. Press Release

Natural Law Party (1998) News Flash! Obtained from:

Powell, C. (November 12, 1998) Beyond Cloning. obtained from: Discovery Magazine WWW Site.

Register Wire Services (February 24, 1997) Cloned Sheep may represent Dawn of New Era in Science. Obtained from:

Svitil, K. (5/20/98) Brave New Genes. Obtained from Discovery Magazine WWW Site.

Svitil, K. (3/2/98) Molly and Polly and George and Charlie. Obtained from:

Wertz, D. (1998) Germ-line Therapy Enters the Foreseeable Future. The Gene Letter. 3(1) Obtained from:

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