1. Genetic engineering study brings warning on tumors
2. Man-beast hybrid beyond talking stage
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1. Genetic engineering study brings warning on tumors
http://sunspot.net/features/health/sns-geneticengineering.story?coll=sns%2Dhealth%2Dheadlines
From Newsday
By Robert Cooke
Originally published September 4, 2001

Efforts to genetically engineer viruses to cure deadly inherited diseases are showing signs of success, along with a new and troubling sign of danger, scientists announced yesterday.

Genetic engineering is seen as a potentially quick, easy and long-lasting treatment - someday. The technique would involve using a virus as a "vehicle" to insert healthy versions of genes into babies born with genetic handicaps, such as Tay-Sachs disease and dozens of others.

According to molecular biologist Mark Sands, his mouse experiments at Washington University in St. Louis were going beautifully last fall when he got a jolting surprise. Of 59 mice in his experiment, six developed fatal liver tumors after they matured into adults. The treatment used viruses to insert a gene to correct an inherited disease called muccopolysaccharidosis type VII, Sly's syndrome.

"It was a total surprise," Sands said about his discovery of tumors in the treated mice. The finding seriously disrupted human trials that were using the virus, called AAV, across the country. AAV is shorthand for adeno-associated virus, a benign virus known to infect without causing disease.

Detailed reports on Sands' results, the liver tumors and another team's success with genetic engineering in mice appeared yesterday in the journal Gene Therapy.

Sands said that after he notified the Food and Drug Administration of his tumor discovery Dec. 7, the FDA briefly halted experiments in Florida, California and Pennsylvania in which engineered AAV viruses were being used or were about to be used in humans.

Now, despite months of study, it still isn't known how or why the few mice in Sands' experiment developed liver tumors. "The bottom line here is that we discovered them, and they are real," Sands said. But "I'm really stumped by this thing."

The discovery is important because AAV is a favorite "vector," or carrier that scientists use to insert new genes into people and animals. In contrast, another virus used as a gene carrier, the adenovirus, causes the common cold. The adenovirus was blamed for the death of one patient, Jesse Gelsinger, in 1999 in a clinical trial at the University of Pennsylvania. The young man's death threw the field into turmoil and stopped some research for months.

"We're appreciative that Dr. Sands called us, even though he's not involved in any clinical studies" with the AAV virus, said Dr. Philip Noguchi, director of the division of cell and gene therapies at the FDA. "He was obviously very shocked when he found this, and of course every investigator using AAV was notified."

Noguchi said two human trials using AAV were under way and one was about to begin when Sands contacted the FDA. The three trials were put on hold, briefly, while officials and scientists assessed all the data they could find from AAV research.

But "we didn't see anything that relates to the ongoing trials" in humans - which were assessing gene therapy for cystic fibrosis and for hemophilia - "so we released the hold," allowing the trialsa to resume, Noguchi said

The two studies under way in humans are being run by Terrence Flotte at the University of Florida to see if it's safe for people with cystic fibrosis to inhale engineered viruses into their lungs. In the Philadelphia study, Dr. Katherine High is injecting AAV into patients' muscle tissue to see if hemophilia can be corrected via gene therapy.

A third human study, in which engineered AAV would be injected into the liver's portal vein, was about to begin at Stanford University when Sands discovered the mouse tumors.

So far, Sands said, the only mice to get the tumors were in his laboratory at Washington University. No problems were found among the mice in Flotte's laboratory in Florida, where mouse and human experiments were under way. It was Flotte who had supplied the engineered virus for Sands' experiment.

Despite the worry about tumors, the gene therapy experiments in mice were producing promising results. Sands said a normal version of the gene that makes an enzyme, beta-glucuronidase, had been inserted by the virus into mice that exhibit almost all symptoms of Sly's syndrome. The disease - caused by the body's inability to process a certain protein - leads to bone deformities, loss of vision and hearing, mental retardation and death.

The new findings do suggest - if the treatment works in humans - that babies born with the genetic disorder may yet become treatable, saving their lives. It also suggests that about 40 similar "lysosomal storage diseases" caused by nonfunctioning enzymes might eventually become treatable.

Flotte and his colleagues at the University of Florida reported similar success at getting functioning genes into mice.
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2. Man-beast hybrid beyond talking stage
http://www.nationalpost.com/tech/story.html?f=/stories/20010822/659629.html
Human DNA in cow egg
by Scott Foster
The Edmonton Journal: NATIONAL POST.

Melding man and beast may sound like the stuff of science fiction, but it's not.  Amid all the advances in genetic manipulation, the idea of combining the DNA of animals and humans has gone beyond the talking stage -- it's been attempted.

Indeed, many scientists and academics are wondering how far it might go and what the ethical implications would be. If a human were crossed with a chimpanzee, for example, would it still be human? And if not, then what would it be?

The first publicized case of animal-human hybrids took place in 1996 when Jose Cibelli, a scientist at the University of Massachusetts, took DNA from his white blood cells by swabbing the inside of his cheek. He then inserted the DNA sample into a hollowed-out cow egg.  Cibelli's experiment came to an end after a week of growing the cell mass, he told scientists earlier this month at a panel meeting of the National Academy of Sciences in Washington, D.C. This raised the question of what might have emerged had the cell mass continued to develop.

"As far as we know, it would still look like a human being, but some of the characteristics of individual cells might be slightly different," said James Cross, a molecular biologist at the University of Calgary who attended the meeting.

If such an embryo could develop, he said, the result would resemble a human mbeing but carry bovine mitochondria, the energy-producing component of every cell. This is because the cow's egg shell, or cytoplasm, contains genetic materials known as mitochondrial DNA.

"This suggests that we can create new human-animal species," said Jeremy Rifkin, biotechnology critic and president of the Washington-based Foundation on Economic Trends.  Rifkin called the experiment "the most extraordinary single development in the history of biotechnology."

Such experiments have become public only when the makers of hybrids, who fund their operations through investor capital, apply to patent their inventions.

In partnership with Massachusetts-based Advanced Cell Technology, Cibelli came out from under a shroud of secrecy in 1998 when the firm applied to patent the alleged invention.

Last October, Greenpeace Germany dug up a patent claim for a similar human-animal hybrid, only this time it involved a pig. U.S.-based Biotransplant and Australia-based Stem Cell Sciences grew a pig-human embryo to 32 cells before ending its life.  "If the embryo had lived, it would be 95% human," said Michael Khoo, a genetic engineering campaigner for Greenpeace's Toronto branch. "The possibilities are not only frightening, but it's unknown just how many other similar patent applications are out there."

Meanwhile, critics and futurists are having a field day speculating on the future of biotechnology.

"Chimpanzees share between 95% and 98% of our genes, so the prospect of creating a human-chimpanzee hybrid are highly probable," Rifkin said. "The question becomes: What percentage of human genes will it take before human rights kick in? Would a hybrid have to look and talk like a human before it can get human rights?"

While the concept of making and owning such a creation for 20 years under patent law is controversial to say the least, the science behind combining animal eggs and human DNA could be useful, said Cross. "In the case of Dolly, it took 277 eggs to get the sheep. In normal IVF programs, the number of eggs you get usually ranges between five and 10. So, to solve a potential shortage, some scientists have considered using an egg from a different species to house human DNA."

While such an attempt to improve the egg supply may be scientifically possible, people are not ready for such a brave new world which involves crossing the species barrier, said Diane Cox, who chairs the medical genetics department at the University of Alberta. "Right now, technology is way ahead of ethics.

The Canadian population is worried enough about relatively trivial things, let alone such a bizarre concept."