Cloning 101

Since 1996, when pioneering Scots cloned Dolly the sheep from an adult sheep cell, scientists have cloned mice, cows, goats, pigs, rabbits, cats, rats, deer, mules, horses, and dogs. Yet despite all the success, cloning remains really, really hard to do. Here’s why.

Coaxing Quiescent Cells

Nature makes clones – genetic duplicates – all the time. We call them identical twins. But twins grow according to the DNA code from embryonic stem cells – cells that are supposed to divide and grow into complete adult beings. Cloners try to get the DNA from adult cells to do the same thing.

Unlike stem cells, adult cells have gone through a process called differentiation. This process allows them to specialize into the muscle, bone, skin, and many other types of cells that make up an entire animal. But it also deprives them of the ability to grow into other cell types. Skin cells can only make more skin cells, and muscle cells can only make more muscle cells. They just can’t do anything else.

Cloners attempt to overcome this specialization by using the DNA from quiescent cells. Quiescent cells no longer replicate themselves, which would seem to make them poor candidates for clonal development. But actually, they’re just what Dr. Clone ordered. The DNA in the nucleus of these cells is in its least active state. Because it’s not busy doing anything, it seems to be more amenable to becoming a clone.

Finding a Host

The next step is to find a suitable host cell from another animal to put the quiescent DNA into. As with donor cells, scientists need to choose host cells carefully. With Dolly, they used sheep oocytes, the cells that go on to form the egg cells used in reproduction.

Of course, most cells already have a perfectly good set of DNA residing in their nucleus. Cloners must remove all this DNA before they can insert the new set. They try to suck the old nucleus out and put the new one in, hoping all the while the rest of the cell doesn’t notice.

Failing Countless Times

Even after successfully receiving a new nucleus, which doesn’t happen often, the vast majority of these cells fail to grow into healthy adults. The host oocyte and the new nucleus need to cooperate. The donor DNA has all the information needed to grow the cell into a complete adult being. But it needs the host oocyte to give it a biochemical “incentive” to do so.

Though oocytes are reproductive cells, supposed to grow into complete adults eventually, this doesn’t always work. Genetic conditions in the nucleus and biochemical conditions in the host cell need to be just right for proper growth to occur. If any one of these conditions is missing or just a bit off, the cell fails.

Getting Pregnant

If the cell does start to divide, growing into the tiny ball of cells that marks embryonic development, cloners face the next hurdle: getting a surrogate mother to accept the embryo. The mother must have a specific set of hormonal conditions that synchronize with those in the developing embryo for it to implant itself in her uterus and grow.

The timing has to be just right. And as anyone trying to get pregnant can tell you, it usually isn’t. The result is a success rate of less than 1 percent. But scientists are learning more every year. Many now believe that any animal could be cloned given enough time, even humans. Whether that’s something scientists should do is another story entirely.

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