September 24, 2022

Will stem cells follow gene therapy into the wilderness?

ll the signs are there, says gene therapy pioneer

In the 1990s, gene
therapy was the Next Big Thing in biotechnology. It was touted for a
huge array of ailments — but it came to a screaming halt in 1999
with the death of 18-year-old Jesse Gelsinger in a clinical trial.
This even changed the life of the scientist in charge of that failed
experiment, James M. Wilson of the University of Pennsylvania.

Now Wilson has
published an essay in Science arguing that stem cell science is on
the same track to disaster: “In today’s clamor of stem cell
enthusiasm it is possible to detect haunting echoes of the early and
ultimately troubled days of gene therapy.”

The same forces
which made him imprudent then exist today, says Wilson.

“Many of the
factors that fueled gene therapy’s premature expansion are major
drivers of the hESC and iPS research agenda today. A large and vocal
population of patients suffering from a wide variety of ailments is
pressing for stem cell–based therapies. Disease-specific stem cell
research groups are more politically sophisticated than ever, in some
cases employing congressional lobbyists. Unrealistic expectations
have been fueled by relentless media coverage, driven in part by a
factor not present in the gene therapy roll-out: a debate over the
ethics of research on human embryos and embryo cells, which has
served as a "news hook" that brings media attention to even
the most incremental of advances.”

He sees the amber
light flashing in Geron’s clinical trial of embryonic stem cells
for curing recent spinal cord injuries. News coverage was remarkable
for its lack of restraint, he says, with the media describing federal
permission to test the cells in patients as a "breakthrough"

In a separate
interview in Nature, Wilson says that he has some serious concerns
about stem cell research in the United States. In the first place, it
is not transparent enough. There is no mechanism for public
disclosure of what is being approved and conducted and there is no
requirement for public disclosure of adverse events.

A number of other
critics of embryonic stem cell research have pointed out that it
could be dangerous, but it comes with more conviction from Wilson.

“Many of the
issues that have caused problems in the clinic for gene therapy are
relevant to stem cells. One is delivery of the cells. Another is
immunogenicity — if you’re using cells donated from another
individual, they’ll be viewed as foreign and cause very complicated
immune responses. The third is that embryonic stem cells may
transform into tumour cells, and there’s already some evidence of
that from one study. The field needs to pay attention to those
areas.” ~ Science, May 8; Nature, May 7