Cloning humans is not going to work until a key problem is solved

As you read this, renegade scientists may have begun an attempt to clone a human being. The Canadian company CLONAID has said it will try this week at an undisclosed U.S. location to clone the world’s first human being, using the DNA of a dead infant. The scientific community has decried the effort, not only for moral reasons, but because the effort is almost certain to fail.

Most cloning efforts fail

Since Dolly’s birth in 1997, scientists have successfully cloned sheep, mice, cattle, goats, and pigs. Only a few per cent of the transplanted embryos survive to term, however, most dying late in pregnancy. Those that survive to be born usually die soon thereafter. Many become oversized, a condition known as “large offspring syndrome (LOS).”

The few cloned offspring that reach childhood face an uncertain future, as their development into adults tends to go unexpectedly haywire. Thus three heifers cloned by scientists at California State University at Chico were born healthy on March 9, but two of the calves died last week of abrupt immune system failure, and the third is failing.

It takes two kinds of information to clone a human

What is going wrong? It turns out that to make a successful human or other mammal, two kinds of information are required:

1. The genome says what proteins are made. The DNA sequences of the genes within an adult donor cell provides the basic information specifying a new human being — what proteins are to be made, and how they are to be used to construct the adult body.

2. Reprogramming says when proteins are made. As human egg and sperm mature, their DNA is conditioned by the parent female or male, a process called reprogramming. Chemical changes are made to the DNA that alter when particular genes are expressed, without changing the genes’ DNA sequences.

How reprogramming works

In the years since Dolly, scientists have learned a lot about reprogramming. It appears to occur by a process called genomic imprinting. While the details are complex, the basic mechanism of genomic imprinting is simple.

A gene, like a book, can have no impact unless it is read. Genomic imprinting works by blocking the cell’s ability to read certain genes. A gene is locked in the “OFF” position by chemically altering some of the cytosine DNA units. Because this involves adding a CH3 cluster of atoms (called a methyl group by chemists), the process is called

methylation. After a gene has been methylated, the polymerase protein that is supposed to “read” the gene can no longer recognize it. The gene has been shut off.

Genomic imprinting can also lock genes in the “ON” position, permanently activating them. This process also uses methylation, but in this case it is not the gene which is blocked, but rather a DNA sequence that normally would have prevented the gene from being read. Each human gene has a battery of helper proteins that boost its expression. In order to prevent a gene from being expressed too early, many human genes use DNA sequences called “insulators” to shield the gene from its team of helper proteins. A bulky protein binds onto the insulator sequence. This prevents the helper proteins from getting near the insulated gene, for the same reason that two people cannot sit in the same seat at the same time.

Genomic imprinting locks such a gene in the “ON” position by methylating the insulator sequence. Now the bulky protein cannot bind to it and shield the gene. No longer blocked, the helper proteins get in, do their job, and the gene is expressed.

Why cloning fails

Normal human development depends on precise genomic imprinting. This chemical reprogramming of the DNA, which takes place in adult reproductive tissue, takes months for sperm, and years for eggs.

During cloning, by contrast, the reprogramming of the donor DNA must occur within a few minutes. After the donor nucleus is added to an egg whose nucleus has been removed, the reconstituted egg begins to divide within minutes, starting the process of making a new individual.

Cloning fails because there is simply not enough time in these few minutes to get the reprogramming job done properly. Lorraine Young of the Roslin Institute in Scotland (Dolly’s birthplace) reported in March, for example, that in Large Offspring Syndrome sheep, many proteins have failed to become properly methylated.

How to successfully clone a human

Human cloning is not going to be practical until scientists figure out how to reprogram a donor nucleus, as occurs in our bodies to the DNA of sperm or eggs. This reprogramming may be as simple as finding a way to postpone the onset of cell division after adding the donor nucleus to the enucleated egg, or may prove to be a much more complex process.

The point is, we don’t have a clue today as to how to do it. In light of this undeniable ignorance, any attempt to clone a human is simply throwing stones in the dark, hoping to hit a target you cannot see.

© Txtwriter Inc.

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