August 27, 2009

Hope, Concern Over New IVF Technique

Researchers believe they have found a way to avoid certain genetically inherited disorders through a special kind of in vitro fertilization (IVF).  Ethical concerns abound, but experts say that the future of the procedure looks promising.

In lab experiments with rhesus macaque monkeys, scientists from the Oregon Health and Science University were recently able to transfer DNA from the nucleus of an unhealthy egg cell into a normal egg cell without a nucleus, ultimately resulting in the births of three healthy monkeys.

The research has inspired hope for those seeking a cure for several rare genetic disorders that result from defective egg cells.

Major ethical hurdles for trials on humans remain, however, as a small number of the genes inherited by the offspring created from the procedure inevitably come from a "third parent."

A number of rare and typically unfamiliar genetic diseases, such as Leber hereditary optic neuropathy, are caused by defective DNA found in the cell's mitochondria.  In recent years, researchers have also linked certain forms of anemia, dementia, hypertension and other neurological disorders to faulty mitochondrial DNA.

While the overwhelming majority of a cell's genetic information is housed inside the cell's nucleus, a small number of genes are found in these tiny organelles that are more commonly known as the cell's "power house." 

Critical to ethical concerns is the fact that mitochondrial DNA is inherited exclusively from the mother.

In the recent US project, featured in the current edition of Nature, scientists were able to selectively extract the nuclear DNA from a monkey egg cell with sick mitochondria and insert it into another egg cell without a nucleus but with healthy mitochondria.  The eggs were then fertilized and allowed to develop, and eventually resulted in three healthy baby rhesus monkeys with no signs of birth defects.

Dr. Shoukrat Mitalipov who spearheaded the project says he would like to see human trials begin as soon as possible.

"It is estimated that every 30 minutes a child is born with this devastating disease and I believe we could prevent that," said Mitalipov.  "Moving to human trials could be very quick, maybe within two to three years."

Dr. Mitalipov has already submitted an application for a research license that would, if approved, allow him to work with human eggs and embryos.

"This type of gene therapy is much closer to clinical application than anything else before," he added.

Not everyone, however, is as gung-ho about the research as Mitalipov and his colleagues.  A number of groups are concerned about the trans-generational ethical problems that could potentially surface from the procedure.

Because mitochondrial DNA is inherited exclusively from the mother in humans, it can potentially be passed down over many generations, meaning that a tiny fraction of DNA could be inherited over and over through a family lineage that did not actually belong to an original family member.

Dr. Helen Wallace of the group GeneWatch believes that this is cause enough to pause and reflect on the possible ethical ramifications.

"The fact that [the] treatment effects would persist for generations means ethical debate is needed, as well as more safety tests."

But Professor Robin Lovell-Badge of the National Institute for Medical Research has attempted to allay such ethical concerns by pointing out the relative ethical and biological insignificance of mitochondrial DNA.

"Mitochondria do not confer any human-specific qualities," he explained.  "It would be similar to changing the bacteria in our intestines, which I suspect no one would care about."

"Altering the nuclear genome is a different matter.  As it would be difficult and risky, there would have to be very good reasons for doing this."

Douglas Wallace, an expert on mitochondria at the University of California seems to see both sides of the issue.

He finds the results of the study exciting and "potentially very interesting," but concedes that "there are safety issues that are going to need to be addressed before one could think about it in humans."


Image Caption: "Mito and Tracker" - OHSU


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