How to genetically engineer humanity

January 28, 2000

Nuclear transfer

After Dolly came Polly. Although she is less famous than her cloned cousin, the techniques used to produce Polly the sheep may be more relevant to germline genetic engineering of humans.

Polly was created from foetal sheep cells that were extracted and grown in culture. A human gene was added to the mix and each cell in which the gene "took" was fused with an egg cell by nuclear transfer - the method used to create Dolly. The embryos were implanted in a sheep's womb and Polly became the first of four sheep born this way, each with the human transgene in every cell of its body.

Such a method could be used to alter cells in the early human embryo to create a genetically modified person.

Germ-cell therapy

Instead of correcting "mistakes" after they happen, why not start with good ingredients? That is the philosophy of Ralph Brinster of the University of Pennsylvania, who has developed a technique in mice for genetically altering sperm. If this technique were developed for humans, a man who did not wish to pass on a genetic defect to his children could have gene therapy on his sperm-producing cells. These could be implanted into mice, which would produce "healthy" human sperm. Eggs fertilised in this way would grow into humans with the new gene in all cells.

Gene 'surgery'

Genes can end up in the wrong place, causing unwanted effects. So why not correct genetic mistakes? Two methods in development would do just that.

The first involves "homologous recombination", making use of a natural process in which a strand of DNA occasionally binds to another strand with a similar sequence and replaces it. Molecular geneticist Dieter Gruenert of the University of California at San Francisco used this technique on a single fertilised mouse egg to correct a genetic "mistake".

The second method is "chimeraplasty", which involves the insertion of a chimera - a DNA-RNA-DNA strand containing a portion of the offending sequence. This technique is being pioneered by molecular biologists at the lab of Eric Kmiec, at Thomas Jefferson University in Philadelphia. They believe the chimera binds to the DNA sequence, "flagging" it for correction by the cell's DNA repair apparatus.

Advocates of germline therapy are pinning their hopes on such techniques for permanently eliminating single-gene diseases such as cystic fibrosis and Tay-Sachs disease.

Artificial chromosomes

Another way round the problem of genes inserting randomly in the genome is to pre-package them in artificial chromosomes.

Human artificial chromosomes have already been created in the lab of Huntington Willard of Case Western Reserve Medical School in Cleveland, Ohio. They could be used to deliver sets of genes, such as those that govern complex traits, including intelligence or athletic ability.

People with artificial chromosomes would need medical assistance to have children. Since they would have a different number of chromosomes from the rest of us, they would be able to mate normally only with one another.

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