As a crusader against reproductive human cloning, Rudolf Jaenisch doesn’t exactly fit the profile. He’s motivated by neither politics nor religion. To make his case he appeals only to biology: human reproductive cloning will never succeed because fundamental facts of biology stand in the way.

“As a scientist I have an obligation to warn against this,” says Jaenisch, an MIT biology professor, a founding member of the Cambridge, MA-based Whitehead Institute for Biomedical Research, and one of the world’s top researchers in the science of cloning. “From a scientific point of view, human reproductive cloning is unsafe and unacceptable.” Reproductive cloning, he argues, shortcuts basic biological processes, making normal offspring impossible to produce. And unlike the early days of in vitro fertilization, he says, this is not a technical hurdle that can be overcome with more advancesit’s a fundamental biological problem.

Jaenisch carefully distinguishes between therapeutic cloning to produce stem cellswhich he believes feasible and supportsand human reproductive cloning. This distinction is missing from legislation passed in July 2001 by the U.S. House of Representatives banning all types of cloning. The bill’s supportersnow pushing a Senate versionforesee therapeutic cloning leading inevitably to reproductive cloning, a view shared, ironically, by cloning advocates such as Yale historian Daniel Kevles (see “Cloning Can’t Be Stopped,” June 2002).

In both therapeutic and reproductive cloning, the nucleus from one cell is removed and placed into an unfertilized egg cell whose nucleus has either been deactivated or removed. In reproductive cloning, after a few divisions the egg cell is placed into a uterus where it will then hopefully develop into a fetus genetically identical to the donor of the original nucleus. In therapeutic cloning, however, the egg is placed into a Petri dish where it develops into embryonic stem cellswhich have shown enormous potential for treating a host of ailments.

Rudolf Jaenisch (Photo courtesy of the Whitehead Institute for Biomedical Research)

The Petri dish and the uterus make all the difference. “It’s a clear dividing line,” says Jaenisch emphatically from behind a desk piled high with papers escaping their manila folders, a clutter that spreads onto the surrounding floor. “So for example, if you take a mammary gland nucleus from a cow, the genes needed for milk production are active, but not the genes needed for embryonic development. They’re present, but they’re silent.” When that nucleus is implanted in an egg, which is then implanted into a uterus, the entire genome in that nucleus needs to be activated. And there lies the rub. The biological problem is a principal onehow do you reprogram the nucleus so that it directs development of a normal animal?

With normal fertilization, the egg and sperm go through a long process of maturation, resulting in two genomes poised to activate the early embryonic genes. But cloning shortcuts that by trying to reprogram one nucleus’s whole genome in minutes or hours. And according to Jaenisch, this process is not faithful. He believes that there isn’t a single reproductive-cloning case in which the entire genome has been thoroughly reactivated. What has been achieved, he says, is everything from gross physical malformations to subtle neurological disturbances. “Most clones die immediately, some die later because of gene malfunction, others die at birth, and very few make it to adulthood. Now we have hard data to argue that these adults are not normal. We’ve looked carefully at adult cloned mice and found that they have significantly shortened lifespan and have, for example, major pathological alterations in their livers.” This holds true, he says, for cows, sheep, and goats.

Jaenisch has even less patience for arguments for reproductive cloning that compare cloning today with the early days of in vitro fertilization. “IV fertilization, when it was invented 30 years ago, was a purely a technical problem. We had to learn how to culture human embryos after fertilization. Now it’s successful. And from the very beginning we knew what we needed to do.” But the biological problem of reprogramming the genome has nothing to do with how skillfully a scientist can place a nucleus into an egg cell, he says. “Technique is important, but it will only improve how efficiently you produce abnormal clones.”

Jaenisch has repeated his warning to congress, to journalists, and repeatedly to his fellow scientists. But, he admits, it is unlikely to prevent them from trying.