1.Investing in gene therapy, despite the latest deaths
2.More on French Anderson the 'father of gene therapy' - 'Who's Afraid of Designer Babies?'

Prof Joe Cummins: "The article below [item 1] provides a very strange metaphor. It quotes a biotechnologist as asking 'there's been an awful auto accident, is there a future for the transportation industry?'.

Comparing gene therapy to the transportation industry is very nutty. In spite of the billions pored into the industry it has never produced anything that works! Biotech is rather like the invention of a square wheel, it really does not work!

There seems to be a sickening philosophy among the gene therapy researchers that the death of a few children and injury of others is a small price to pay for large grants and high salaries among the elite researchers."

For more on the abuse charges faced by French Anderson [the subject of item 2] see:

Quote from French Anderson: "...we realised that, that we just didn't know enough about what was going on, that the body had reactions, had defences that we didn't really understand, and it really required going back and really rethinking everything we were doing." (item 2)

1.Under the Microscope again
Some investors show new interest in gene therapy, despite the latest scare
By Clare Kittredge
The Scientist [shortened]
Volume 19 / Issue 9 / 15 / May 9, 2005

The tally is grim: three high-profile cancer cases, including one death, in French boys who underwent pioneering gene therapy for X-linked severe combined immunodeficiency (X-SCID). Yet Edward Lanphier is upbeat about the future of gene therapy.

"It's a very, very broad field," says Lanphier, CEO of Sangamo BioSciences, a Richmond, Calif., biotechnology company focused on gene regulation. "It's sort of like saying there's been an awful auto accident, is there a future for the transportation industry? Is there a future for gene therapy? Categorically yes. Will companies pursue this from a commercial perspective? Categorically yes. And the outcomes in France in some of the SCID trials, as tragic as they are, are extremely informative."

Lanphire was reacting to the latest setback in a field that has experienced dramatic lurches in the last two decades. Gene therapy, once hyped as offering boundless promise by fixing faulty genes, has seen some dark days. Yet some financial experts observe renewed investor interest in the field, and many scientists and CEOs say the technology is now too diverse to paint with the same broad brush.

"Gene therapy is not gene therapy is not gene therapy," says Rich Gregory, head of research for Genzyme in Cambridge, Mass. "Of course the French case has an impact because everybody understands these are issues associated with gene therapy, but from a pure technological point of view, many companies would say it does not relate to what they're doing."


Hopes for gene therapy soared in 2000 when Marina Cavavazzana-Calvo and Alain Fischer of the Necker Children's Hospital in Paris reported successfully using gene therapy on children afflicted with X-SCID. However, a boy treated by Fisher was diagnosed with a leukemia-like cancer in September 2002, and a second boy was diagnosed three months later. One of the boys died in October 2004, and a third was diagnosed in early 2005. Other children who are now free of X-SCID because of the treatment, including some in France and the UK, are being monitored. In late January, the Food and Drug Administration suspended three similar gene therapy trials in the United States.

Jean-Yves Bonnefoy, chief scientific officer of Transgene, a biotechnology company based in Strasbourg, France, says his company has largely moved away from gene therapy, although the move pre-dates the French cases and has more to do with seeking a larger market. "The problem with gene therapy is the targeting and delivery vehicle," say
Bonnefoy, worked with Fischer in the early 1990s. "How can you make sure it targets only the cell you want?"

Other high-profile gene therapy cases have not helped, such as the death of teenager Jesse Gelsinger in a 1999 trial at the University of
Pennsylvania. Some experts say his death was due to the high number of viral particles infused during the trial, rather than the gene therapy itself.

All this has investors cautious about betting on gene therapy.

Navdeep Jaikaria, director of equity research for the New York City investment firm of Rodman & Renshaw, says companies targeting a narrow spectrum of the field may be successful, although gene therapy has "definitely fallen out of favor with investors."

"You can measure that by the value gene therapy companies are enjoying compared to other similar-stage biotech companies. They are trading as a
group at a 30% to 40% discount," Jaikaria says. "Avigen recently announced that it is discontinuing its gene therapy program."

However, the situation could change rapidly. "Any success can bring investors back. We like companies addressing unmet medical needs like cancer and cardiovascular disease, because the risk-reward profile is such that the FDA is willing to look at novel therapies," says Jaikaria. "We view gene therapy to be no different from any other drug delivery platform, but there are questions which keep investors concerned."

Jaikaria says companies focusing on short-term gene therapies show commercial promise. "There are two kinds of gene therapy, if you can say that in a simplistic manner. One is you put a gene into a cell and it doesn't integrate with the genome of the individual, and that's what GenVec and Coratus [Genetics] and several other companies are trying to do. The other form of gene therapy is trying to correct a deficient gene in a cell, and we don't really see that kind of gene therapy succeeding
commercially in the next five to 10 years. But GenVec, Coratus, Targeted Genetics, Sangamo we think they have promise and their programs can succeed."

Genzyme's Gregory says the French clinical trials have caused a public-relations problem for gene therapy in general, and they have affected small companies' ability to raise money. "It's tough for companies in the gene therapy space to raise additional funds because of the general impression in the venture capital community that gene therapy is not the place to be," Gregory says. However, the trials have had less impact on Genzyme, which has a long-term commitment to gene therapy and still sees it as a therapy of the future. "For us, it's been steady, hold-the-course, but I can see there are certainly fewer companies in the gene therapy space than there used to be, and my impression is it's tougher for those companies."

2.Who's Afraid of Designer Babies?
BBC TV: Horizon
*excerpt from programme transcript*

French Anderson has been hailed as one of the most remarkable scientists of our time. He pioneered what claimed to be the biggest revolution in modern medicine, treating genetic disease by inserting healthy genes into patients. It's called gene therapy.

Dr FRENCH ANDERSON: ...The key cells that we really want to get genes into are the so-called blood stem cells, because these are the cells which continue to repopulate the blood system for our whole lives. Some of our blood cells only last a few hours, some last a few days, some last a few weeks. But basically they're constantly turning over, so we need to get genes into that original stem cell that will, that will, that reproduces the bloo system.

NARRATOR: Anderson thought he might be able to get into these stem cells by injecting the healthy genes directly into a foetus in the womb. In theory, if the new genes made it into the blood stem cells, the foetus would then create it's own cells with healthy genes forever. It would be cured. It seemed the perfect solution, and in 1998 he decided to make it public.

Dr FRENCH ANDERSON: And so we brought this to the government regulatory committees basically three years before we anticipate being ready to actually do a clinical protocol. And as expected, there was considerable interest in this topic, as we did not expect there was a considerable amount of hysteria about this topic.

NARRATOR: The hysteria was caused by these mice. New genes were inserted into them when they were just embryos. Effectively a form of gene therapy on the unborn mice.

Dr LEE SILVER: The very first gene that was added to an embryo was a gene coding for growth hormone. It's a gene that causes an animal to grow larger. And a growth hormone gene from a rat was placed into a mouse embryo and when the mouse was born and it grew up it grew to twice the size of a normal mouse. This had a horrifying incredible effect on society at large. I mean this was the first instance of genetic engineering actually occurring in an animal.

NARRATOR: What's so sinister about these mice is that the new gene had been copied into every single cell of their bodies, including the eggs and sperm. So, crucially, all their offspring would also be giants. The scientists had altered their so-called germ line forever, creating a new breed of designer mice. French Anderson had no intention of altering the human germ line. He only wanted to cure disease. But by introducing the genes at such an early stage of development, no one could be sure that the genes wouldn't enter the germ line as well. And if they did, his treatment would lead to a never-ending line of genetically engineered humans. For Anderson, the goal of curing sick children made it a risk worth taking.

Dr FRENCH ANDERSON: Many people seem to feel that our honest statement that there might be a very low level of inadvertent germ line gene transfer might really be hiding that we're trying to get into the germ line, we're trying to redesign babies.

NARRATOR: But for others even an accidental change to the germ line could not be dismissed easily.

Dr PHIL BEREANO: It's immaterial whether he intends it or not. Society has to deal with the reality of the consequences and whether this one person intended those consequences or not is immaterial to the, either the ethical issue or, or the social reality of what's going to be produced from them.

Dr LEE SILVER: The problem is that once we tinker with the genes and the sperm and the egg we give somebody the ability to be able to pass on these new genetic elements that have never been present in human beings before and they get passed on to the generation, next generation. They can get passed on to generation after generation for untold number of generations and so in a sense it gives us the ability to completely change the human species.

NARRATOR: The stage was set for a mighty ethical battle. Anderson was convinced that foetal gene therapy could work and was responsible. Set against him were moralists and some scientists who feared it would lead to designer babies. But in the end it all came to nothing. The difficult part of gene therapy had always been getting the healthy gene into a cell. Anderson had used a virus. These viruses had been modified so that they wouldn't cause an infection, as they transported the healthy genes inside the cells. In other clinical trials, these modified viruses also seemed to be working. But then one gene therapy trial, in Philadelphia went dramatically wrong. Jesse Gelsinger had been injected with a modified cold virus as part of a gene therapy treatment. But the virus was not as safe as scientists had thought. Within a week it had attacked all his major organs and he died.

NEWS CLIP: Medical detectives have now concluded that an 18-year-old is the first known person ever to die as a direct result of gene therapy.

Dr FRENCH ANDERSON: When Jesse died it just stunned all of us, it just, it just, we realised that, that we just didn't know enough about what was going on, that the body had reactions, had defences that we didn't really understand, and it really required going back and really rethinking everything we were doing.

NARRATOR: Jesse's tragic death changed everything. It was clearly far too early to think about using this potentially dangerous technique in the womb.