How to make enhanced male sperm

Of course, biotechnology never stops, especially if you thrown in some spicy nanotechnology. If we can fix male sperm, that is fix any defective genes, why not throw in a few extra genes so that your children have an extra advantage (for example, add in a gene that gives them more connections between their brain cells) or to make your children easier to locate at night (by adding the gene for Green Flourescent Protein so that they glow in the dark - it works for bunny rabbits - the infamous GFP Bunny . Now I suspect some of you are mentally shrieking at this point, but save that for the Ethics page on this Web site.

Instead, on this Web page is an explanation of how to enhance male sperm. You may be wondering what the relevance of this is to female sperm. Well, in some cases, it is possible to make sperm for a man who has no sperm. The question arises - is it then possible to make sperm for a non-man who has no sperm - a woman? Stay tuned.

From earlier Web pages, making and fixing male sperm is a six step process, with the fifth step having a four stage introduction: CREATE, LOCATE, COOK, SIMMER, DAZZINGLY SPLIT (to fix: first EXTRACT, ZAP, FIX, REPLANT) and the ASSEMBLE. To enhance the male sperm, we alter the FIX stage to be the FIX-or-ADD stage. That is, to the extracted germ cells we ADD new genes, either simply injecting them in with minimal packaging, or to insure stable transmission of the added genes in descendants, we add to the extracted germ cells the extra genes packed in one of the wonders of nanotechnology, artificial human chromosomes.

On this Web page, we will review this ADD process. We will review techniques for adding genes to germ cells using chromosome transfer and artificial chromosomes.

ADDING GENES TO SPERM CELLS USING ARTIFICIAL CHROMOSOMES

One way to add genes to a cell is to inject the genes into cells for therapeutic purposes, a process known as gene therapy. The U.S. Department of Energy's Humane Genome project has a nice introduction to gene therapy. But such injections are haphazard in that it is hard to target the placement of the gene to a specific region of a particular chromosome. Human gene therapy is constantly improving, but for something involving human procreation, it would be better to have a procedure that offers more control.

For stable germ line engineering, one wants to add extra genes in a very controlled manner using a fully component cellular component/ Now adding DNA to existing genes in the regular human chromosome set is very tricky and often very random, like throwing very very very small darts (the DNA) and very very very small targets (the chromosomes). It would be nice if we could create a new chromosome with just the added DNA in it, and then add the new chromosome to the germ cells (which is much easier to do than adding DNA to an existing chromosome). Now you may be thinking, hey you guys, stop writing this science fiction, but it just isn't so.

An alternative suggests itself from animal genetic research - artificial chromosomes. Human genetic material is stored in 23/26 pairs of human chromosomes, which comprise the genetic material, packaging and some controls. So what to do? Well, this is America, and when we can't have the real thing, we go artificial. So why not create an artificial chromosome that carries the genes we want to add? Indeed, since the 1990s, a variety of research efforts around the world have been focused on producing one of the wonders of nanotechnology, a human artificial chromosome (usually referred to as a mammalian artificial chromosome). Artificial chromosomes have been known for decades for lower life forms (yeast artificial chromosomes, bacterial artificial chromosomes), but you really want to have human artificial chromosomes if you are going to add DNA to human cells.

What is a chromosome? - Most of a chromosome is DNA - your genes plus filler material. At the end of the chromosome are protective caps known as telomeres (kind of like those plastic caps at the ends of your shoelaces). Chromosome have central hubs, centromeres, to anchor the DNA. And chromosome have Origins-of-Replication (ORIs), a sequence of genetic instructions that allows the chromosome to copy/replicate itself.

Many years ago, scientists proposed a variety of approaches to making artificial chromosomes: remove DNA from existing chromosomes, induce cells to generation empty chromosomes, or chop up and reassemble chromosomes minus the DNA. You would have generic empty chromomsomes. If you could selectively add genes (such as sperm making genes), you would have a human artificial chromosome - a HAC (more commonly referred to as mammalian artificial chromosome, MAC, but let's face it, it is the human application that is of most fun and profit). This idea was not that strange, since yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) were already being used. But these types of artificial chromosomes have parts from non-humans (though as compared to humans with pig valves in their hearts), and can carry only small sized genes, a problem for some of the large human genes one might want to place inside a HAC.

A group of Hungarian scientists (whose work is now commercialized by a Canadian company) have induced cells to generate human artificial chromosomes. They generate human satellite DNA-based artificial chromosomes (SATACs - hilarious acrohym) by amplification-dependent de novo chromosome formations induced by integration of exogenous DNA sequences into the centromeric/rDNA regions of human acrocentric chromosomes. Such chromosomes can be made and purified in quantity, can carry large sequences of DNA, and can be transferred into cells and embryos of differenet species.

One group of scientists, originally based in Hungary, and now at the Canadian company Chromos, have been pursing this line of research and product development. Click here for an overview of their technology, or a local copy.

While human artificial chromosome product development is in its infancy, there enough fun and profit in their use for research and development to continue. And one application of all of this R&D will make to help facilitate the creation of female sperm.

An interesting connection between germ cells, aging and cancer. Most cells divide a certain number of times and then die. This is due in part to the protective ends of the cells' chromosomes, the telomeres, shortening as the cell ages. Cancer cells, which don't age, have the length of their telomeres maintained (???). Interestingly, male and female germ cells also do not shorten over time, with the cells maintaining a high level of a chemical, telomerase.

WILL ARTIFICIAL CHROMOSOMES BE INHERITED AND WORK?

Some experiments to date indicate yes.