In early 1996, an analyst at Salomon Brothers investment firm, detailed like
never before the "unrecognised potential of xenotransplantation": a $6 billion
market in transgenic organs by 2010. The report was read by big and small
investors alike--biotech venture capitalists (who pumped money into
xenotransplant research), as well as newspaper personal investment columnists
who featured companies like Imutran, Nextran, Alexion, and
BioTransplant as "hot picks." In these heady times, some companies were
even suggesting that we might each have our own Astrids, "self pigs"
custom-made from our own DNA, "immunological twins" available for any spare parts we might need in the course of our lives.
Some five years later, the big profits have not yet been realized. In late 2000, a number of the original players in the xeno business reorganized their
efforts for the next phase of research and development: Most notably,Novartis, the Swiss pharmaceutical giant,
merged Imutran with BioTransplant to form a new company, Immerge
BioTherapeutics; the new company is allied with another Novartis-funded
company, Infigen, for use of Infigen's patented cloning technology. While
this move was said to reflect a new commitment to xenotransplanation by
Novartis, another company's "refocusing" seemed to start with a vote of no confidence
for pig-to-human transplants: In August of 2000, PPL Therapeutics, a Scottish company that set out to commercialize the "Dolly" cloning technology,
lost "considerable funding" for its xenotransplantation program from Geron, a California-based company that had been PPL's largest xeno backer. PPL and Geron both denied that the move should be construed as any kind of judgement on the viability of pig-to-human transplants, but PPL has had difficulty finding a new partner for its xeno program.
Here's a look at the major players in the xeno business, past and present:
This small biotech start-up in Cambridge, England took the early lead in the
race toward the organ farm: In December of 1992, at a farm in Cambridgeshire,
they created "Astrid," the world's first transgenic pig, who carried human
genes within her organs to help prevent rejection by the organ recipient's
immune system (one of the thorniest problems facing xenotransplantation). A
year and half later, Imutran announced it had produced several generations of
Astrids who might be eligible for human trials by 1996. Started by a handful
of scientists, the company received early funding from Sandoz pharmaceutical
company whose profits were heavily derived from an immunosuppressive drug key
to successful transplants. Sandoz eventually purchased Imutran outright. In
1996, Sandoz merged with Ciba-Geigy to form Novartis.
In January, 2001, Imutran completed the relocation of its xenotransplantation
research to Charlestown, MA, combining with BioTransplant (another
Novartis-funded company) to form Immerge BioTherapeutics. The company
denies that the move was motivated by animal rights protests in the UK.
In the early 1990's, a small biotech company in Princeton, NJ--the DNX
Corporation--emerged as one of Imutran's chief rivals. Using a farm in Albany,
Ohio, Nextran successfully produced transgenic pigs whose hearts survived for
impressive lengths of time in baboons; they were also far along in developing
pig livers as filter "bridge" organs for people awaiting transplants. In late
August, 1994, the Baxter Health Care Corp. of Deerfield IL partnered with DNX
to form a new company--NEXTRAN--with Baxter owning 70% of the partnership. At
the time of the formation of Nextran, Baxter's biggest revenue-generator had
come from its dialysis equipment, so it took a special interest in DNX, which
had been developing transgenic kidneys that might one day make dialysis less
necessary. In 1995, Nextran became the first to win FDA approval for human
clinical trials involving transgenic pig livers.
In FRONTLINE's report, a Nextran pig saved Robert Pennington's life. It
was used outside his body as a temporary "bridge" to filter Pennington's blood
while he waited for a human liver transplant. Nextran also is involved in
trying to solve the problem of hyperacute rejection problems facing pig-to-human transplants.
Formed in 1992 by a group of Yale University scientists, Alexion was one of the
early innovators in finding transgenic solutions to hyperacute rejection in
transplant organs. Though initially focused on creating organs (their pigs
were grown on farms in West Virginia and Massachusetts, Alexion has had some of
its greatest success with implantation of pig nerve cells to repair spinal cord
damage. In late 1998, Alexion made headlines worldwide for successfully
repairing severed spinal cords in rats and monkeys using pig cells. Alexion's
clinical trials continue.
Based in Edinburgh, PPL Therapeutics is licensed to commercialize the cloning
technology pioneered by the Roslin Institute which surprised the world in 1997 with its
creation of "Dolly," the first cloned mammal. In 1998, the company moved its
xenotransplantation program to Blacksburg, West Virginia where scientists
affiliated with Virginia Tech University were already involved in the research.
In March of 2000, PPL's Blacksburg laboratory announced the creation of the
world's first cloned pigs. (Later in the year, Wisconsin-based Infigen would be
the first to clone transgenic pigs; these pigs were first shown
nationally in FRONTLINE's report.)
In August of 2000, PPL Therapeutics' xenotransplantation program lost
"considerable funding" from its major backer, Geron
corporation of Northern California, who cited a change in "strategic priorities" and a
desire to concentrate on stem cell work. PPL executives as well as the
director of Edinburgh's Roslin Institute issued press releases denying that the
Geron move was a vote of no confidence for xeno: "The institute has had a
research programme on pig cloning, one application of which would be the use of
pig organs for xenotransplantation. While xeno has raised a number of
well-publicised issues, such as possible infection with pig viruses, these were
not the basis for the decision to refocus the funding." ). PPL continued to
look for partners through the Fall of 2000, but negotiations broke down, largely due to questions about the value of PPL's xeno program.
In early 2001, PPL's Blacksburg, VA lab announced that it had secured
new funding--not for xeno, but for stem cell research. It's too soon to tell
whether this is one company's story, or a cautionary tale for the industry.
Founded in 1990 and taken public with a stock offering in 1996, BioTransplant
was one of the early pioneers of xenotransplantation. Like their rivals,
BioTransplant focused on overcoming the hyperacute rejection problem, basing
their approach on the bone marrow research of Dr. David Sachs. In August,
2000, the company, which is partnered with Massachusetts General Hospital,
announced a breakthrough in breeding transgenic pigs that would not transmit
pig viruses, or PERV's.
In January of 2001, BioTransplant spun-off its xenotransplantation program,
partnering with Novartis (and the former Imutran) in a new company, Immerge
BioTherapeutics, but keeping their offices in the Charlestown Naval
Infigen was created in 1997 to commercialize the animal cloning techniques developed
at American Breeder Service (ABS Global Inc.)--a DeForest Illinois company
which is part of W.R. Grace. (ABS describes itself as "the world's leading
provider of bovine reproductive services and technologies," a global marketer
of dairy and beef cattle semen.) In January of 1999, Infigen and Imutran (Novartis) formed a
working alliance that guaranteed Infigen's funding in exchange for use of the company's patented nuclear transfer cloning techniques.
In his FRONTLINE interview,Michael Bishop
PhD Infigen's president, explains how genetically modified pigs can be created and cloned.
Founded in 1990, Diacrin became a public company in early 1996, after
the FDA gave the company approval for the first-ever clinical trials of
transplanted pig cells into humans. Later in 1996, Diacrin entered a joint
venture with Genzyme to develop two products using pig neural cells. .
On March 16, 2001 Genzyme and Diacrin reported that a preliminary analysis of
outcomes of Phase II trials for Parkinson's patients found pig neuro cell
transplants did not necessarily work better than a placebo treatment. The
results are likely not the end of the research trial, but the news triggered a
significant drop in stock prices. Jim Finn, a Parkinson's
patient featured in FRONTLINE's report, was part of a Phase I trial. Other
Diacrin/Genzyme Phase I patients featured in FRONTLINE's report--Maribeth
Cook and Amanda Davis--were stroke patients.
Beginning operations in January of 2001, Immerge BioTherapeutics is a new
company formed from the UK's Imutran and the xeno division of the Boston-based
BioTransplant company. Unlike the companies from which it was formed, Immerge
is focused squarely on development of cells, tissues, and organs for
xenotransplantation, and not on drug therapies or other transgenics.
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