Are Designer Babies a science of the future?

Could you imagine a world where not only your birth being planned but your also your phenotypic makeup like hair and eye color.  Don’t worry because this is a far shot down the road, but the technology to selectively choosing embryos with  a greater chance of developing into a healthy human being is practically already here.

The  two methods to “design” some aspects of a human before birth that I will talk about are PDS and Germline Genetic Engineering . The first which is currently in practice and less controversial is Pre-implantation Genetic Diagnosis and Screening(PDS). PDS is a two step process in which several embryos are developed in a lab,via in vitro,to an eight cell stage. Then, two cells are removed from each embryo and the genome of these cells are examined to see if they carry the defective gene. Each cell only has one copy of its genome so Polymerase Chain Reaction(PCR) is used to amplify the DNA. However, a phenomena known as allele drop out seriously compromises the reliability of PGD as a heterozygous embryo could be diagnosed as affected or unaffected depending on which allele would fail to amplify(Alex Garvin). Embryos that are found to be free of the genetic defect in both cells are then implanted into the mother and brought to term.

Those embryos that are found to be defective are discarded. But isn’t removing those cells dangerous? Actually we humans are Deuterostomes which means during embryonic development we show indeterminate cleavage which means the development of each cell is not dependent on its parent cell. If cells are removed from the the embryo, the other pluripotent cells will compensate for them; the removed cells can still form a separate small larvae. So, removing one or two cells from the embryo usually isn’t harmful. This method of genetic selection is less controversial since it doesn’t actually involve changing of the genome but rather selecting those most fit to survive.

The second way to design a baby is through germline genetic engineering. This is not to be confused with somatic genetic engineering which targets already differentiated cells of a living person without affecting the sperm or egg cells. These changes to the genome can not be passed to future generations. However, in germline genetic engineering, which is the basis of designer babies, makes changes to the genome that will be passed on to future generations. In this process the embryonic stem cells (ES) from an early embryo or blastocyst are removed. These ES cells are then transfected with modified DNA known as a targeting vector. The cells are transfected via a subset of retrovirsuses. HIV is also part of this group which is known to integrate the DNA it contains into the genome of the host. In this case the host is an ES cell. After the DNA reaches the nucleus of the cell, via retrovirus, it finds and repairs a gene using a gene targeting technique known as Homologous Recombination. The cellular machinery for homologous recombination allows the targeting vector, or modified gene, to find and recombine with the target gene. This is possible because the modified gene still has nucleotide bases that are homologous to the endogenous DNA of the ES cell. This will allow it to precisely align at the correct locus in the genome like chromosomes align during meiosis. Besides aligning to the homologous DNA the modified bases of the gene must also be inserted into the genome. This is achieved in a process similar to crossing over which occurs during the zygotene stage of meiosis I(VcBio).  Insert Diagram of the process -A. Boigny 7/5/09 7:17 PM

The corrected regions, between the homologous sequences, replaces the equivalent regions in the host DNA when the two strands are paired. The homologous recombinant technique essentially repairs “unwanted” DNA in the genome of the ES cell. This technique is what allowed Mario R. Capecchi, Martin J. Evans and Oliver Smithies to jointly receive the 2007 Nobel Prize for medicine when they first did this with mice. Although this technique seems flawless in theory most cells fail to even take up the targeting vector. A few cells even decide to have the vector inserted but at a random locus which can cause several problems from disrupting the function of another gene to activating an oncogene. Only very few cells actually navigate to the correct locus and carry out homologous recombination. However, the very few that recombine correctly in the desired locus can be isolated and grown in colonies to produce significantly more ES cells that contain the modified gene. Now, after the process of creating the genome of the designer baby is achieved, the nucleus of a genetically modified ES cell can then be inserted into a mature ovum that has had its nucleus removed. Then, the embryo may be placed in the mother to develop as a normally fertilized egg would(Nobel Prize).

This document was written in July 5, 2009 and due to a recent discovery may not be portray best method of selectively choosing genes. However, the information here is still accurate to my knowledge.

Sources and citation:

http://www.actionbioscience.org/biotech/agar.html

(really good article about designer babies and several possible questions that can draw ideas)

http://www.NaturalNews.com/z001337_genetic_engineering_civilization_evolution.html

http://www.hgalert.org/topics/hge/noToGE.htm
(an article that is against the practice)

http://www.brighthub.com/science/genetics/articles/22210.aspx (part 1)

http://www.infertile.com/infertility-treatments/pgd.htm

(VIDEO info on the process of PGD and PGS)

• http://nar.oxfordjournals.org/cgi/content/full/33/18/e158
• (gene knock-in techniques..promoter trap technique)

http://www.sciencedaily.com/releases/2009/06/090605123237.htm
(the so called “Warrior Gene” was discovered. a mutation in this gene is said to be a “predictor” of who will join gangs and commit violent crimes!! slippery slope…)

http://www.ibridgenetwork.org/warf/promoter-trap-plasmid-for-identifying-promoters
(better explanation of the promoter traps exact process)

http://www.jbc.org/cgi/content/full/283/17/11244
(more info on target gene knockout)