Health & Medicine / Genetic Engineering

Artificial chromosomes like these could be used as Trojan horses to sneak useful new traits into the human genome.

Genome Biology

Embryos From the Palm of Your Hand
In as little as five years, scientists may be able to create sperm and egg cells from any cell in the body, enabling infertile couples, gay couples, or sterile people to reproduce. The technique could also enable one person to provide both sperm and egg for an offspring—an act of “ultimate incest,” according to a report from the Hinxton Group, an international consortium of scientists and bioethicists whose members include such heavyweights as Ruth Faden, director of the Johns Hopkins Berman Institute of Bioethics, and Peter J. Donovan, a professor of biochemistry at the University of California at Irvine.

The Hinxton Group’s prediction comes in the wake of recent news that scientists at the University of Wisconsin and Kyoto University in Japan have transformed adult human skin cells into pluripotent stem cells, the powerhouse cells that can self-replicate (perhaps indefinitely) and develop into almost any kind of cell in the body. In evolutionary terms, the ability to change one type of cell into others—including a sperm or egg cell, or even an embryo—means that humans can now wrest control of reproduction away from nature, notes Robert Lanza, a scientist at Advanced Cell Technology in Massachusetts. “With this breakthrough we now have a working technology whereby anyone can pass on their genes to a child by using just a few skin cells,” he says.

Gene Targeting
When we create egg and sperm on demand, we may not have to pass along our complement of genes as is. A process known as homologous recombination could allow us to remove undesirable traits and replace them with helpful ones, one gene at a time. Homologous recombination occurs naturally during sexual reproduction, when DNA from the two parents mixes to form offspring that are genetically unique. But as Mario Capecchi of the University of Utah, Sir Martin Evans of Cardiff University in Wales, and Oliver Smithies of the University of North Carolina proved in 2007 with their Nobel Prize–winning work on mice, homologous recombination can also be achieved in the lab. By selectively adding or deleting stretches of DNA in the (artificially) fertilized cell, scientists could knock out genes for a disease like diabetes or insert genes coding for extra height or intelligence.

Artificial Chromosomes
Changing an offspring’s DNA gene by gene can be tedious. A speedier route would be to introduce a multiplicity of new traits all at once by inserting an entire new chromosome, a structured strand of DNA containing many genes. Several researchers, including genetics pioneer J. Craig Venter, have already constructed centromere—work together. The centromere contains proteins that control the delicate process of cell division. How it does so is “an extremely difficult problem,” says Bill Earnshaw, a cell biologist at the Institute of Cell and Molecular Biology at the University of Edinburgh in Scotland. In part that’s because in order to study the centromere’s functions, researchers have had to use techniques that kill the cell. Earnshaw, along with colleagues from the National Institutes of Health and the University of Nagoya in Japan, have finally found a way around the problem and are now conducting the foundational research needed to build functional artificial chromosomes.

Earnshaw believes the synthetic chromosome could eventually be used to shuttle genes like a kind of Trojan horse. Some of those genes, he speculates, could convert ordinary cells into stem cells that might reseed the immune system, aid in rejuvenation, and more. Once the genes were delivered, the centromere needed for that chromosome to survive could be turned off. In subsequent generations, some cells would contain the extra chromosome, and these would be discarded because of their potential to become cancerous. Other daughter cells would not have the reprogramming genes.

“Based on what we know, the artificial chromosome is going to be the best way to modify the genome,” says Lee Silver, a professor of molecular biology and public policy at Princeton University. “Nature doesn’t care about individual children. Instead of rolling the dice, why don’t we take the dice and put them down in the way that parents think is best for their children.” He anticipates the development of specialized artificial chromosomes—a “good health” artificial chromosome, for instance—that could routinely be inserted into human embryos. “You could create a generic version that has lots of good genes like the ones known to protect against cancer, strokes, and heart disease,” Silver says.

Our Post-Darwinian Future
Pluripotent stem cells, gene targeting, and artificial chromosomes could leapfrog over evolution and let us take control of our genome, maybe even turn ourselves into a whole new species. “There is no scientific basis for thinking that we couldn’t,” Silver says. “There’s nothing really special about the human genome. There’s nothing that says this is the end.”

Bioethicist John Harris of the University of Manchester in England, a member of the Hinxton Group’s steering committee, believes that achieving our potential “might require some deliberate changes” to our genes. He predicts that genetic engineering will eventually lead to what he calls “enhancement evolution.” Through the nuanced use of biotechnology, enhancement evolution will gradually introduce genes that improve the species, one person at a time. At that point, deliberate selection will replace natural selection as the driving force for species change. “We are not suited to survive designed as we are,” Harris says. “We are hugely vulnerable to diseases, and new diseases come along all the time. It’s amazing we haven’t been entirely wiped out by one.”

The first changes to the human genome, Harris believes, will happen within small test populations. This will allow us to assess the risks and benefits of the modifications and then decide how to proceed. “It will be an experiment,” Harris says. “You do it for a time, and if it looks good and doesn’t have any disastrous consequences, you continue it. We’ll have plenty of time to manage it in that way.”

Enhancement evolution has plenty of critics. Lanza, for one, is uneasy about giving parents the power to design their children’s genomes. What if a couple wants a world-class athlete in the family and provides those genes, but the child grows up wanting to play chess, he asks. And what if some of the modifications go seriously wrong? Who should have the final say on when and how the human genome should be changed?

On the other hand, if technology can enable us to eliminate disease and disabilities from our children or insert genes that might make them smarter or better looking, why wouldn’t we use it? As DNA guru James Watson once said, “Evolution can be just damn cruel.” At least it is today. Tomorrow the responsibility for evolution may rest on our own shoulders—for better or for worse.

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