LEADING EDGE
THE FUTURE OF
GENE THERAPY
Eventually, gene therapy will
become a staple of 21st century
medicine. But some experts say
society will be better served if
medical researchers proceed
more slowly and prudently.
BY JACK McCAIN
Senior Contributing Editor
I
n its current manifestation, gene therapy is an elegant concept crudely executed. That’s not an indictment — that’s just the way it is for an extraordinarily complicated technology still in its
infancy. After all, it has been only 5 years since the concept of gene therapy was convincingly demonstrated
to provide, if not a cure, then at least a long-term therapeutic effect for X-linked severe combined immunodeficiency (X-SCID) disease.
(Here, gene therapy is defined as the introduction of
genetic material via techniques of molecular biology
into somatic cells [in contrast to germ cells] to treat or
prevent disease.)
RELATIVELY BRIEF HISTORY
Many people still are under the impression that
gene therapy’s proof-of-concept was demonstrated as
early as 1990. For example, on Jan. 26 of this year, the
Los Angeles Times wrote that W. French Anderson, MD,
was “dubbed ‘the father of gene therapy’ after a team
he led in 1990 cured a hereditary disease of the immune system in a 4-year-old girl.” That’s not quite the
way it happened.
Anderson did indeed gain renown for heading the
team that in September 1990 carried out the first gene
therapy clinical trial approved for use in a human. The
goal of this phase 1 study was to define the safety issues involved. The 4-year-old girl had a genetic disease
called adenosine deaminase (ADA) deficiency, which
is caused by a defective gene for the enzyme ADA, re-
sulting in SCID. Via a modified retrovirus, normal
ADA genes were transferred to T lymphocytes that had
been removed from the girl’s body and grown in culture. The white cells then were returned to the patient. In January 1991, a 9-year-old girl underwent the
same procedure.
Today both patients are alive and doing well, but
conventional therapy (pegylated bovine ADA, or PEGADA) given before, during, and after their gene therapy confounded the results and makes any claim of
“cure” based on the gene therapy problematic. One patient has an ADA level that is 25 percent of normal with
the therapeutic gene present in 15 percent of her
peripheral blood mononuclear cells. The other has an
ADA level that is less than 5 percent of normal, and the
“The concept of fixing a broken gene is now entrenched
in medicine,” says Theodore Friedmann, MD, director of
the University of California–San Diego Program in Gene
Therapy. “[It’s] a real field, with many ups and downs behind it and surely more ahead. Its technology is evolving,
slowly but certainly positively.”
1953 discovery of the structure of DNA with a special
issue about genetics, again featuring Anderson. Ever
the optimist, Anderson looked 50 years ahead and
told Time, “By 2053, there will be a gene-based treatment for essentially every disease. Cancer, heart disease, and other modern-day scourges will be vastly reduced.”
Halfway through Anderson’s 20-year window (but
barely into his 50-year projection), you can count the
number of clearly effective gene transfer therapies in
nonexperimental clinical use with your nose. That’s
right — there’s one. And you have to go halfway
around the world to get it.
In October 2003, in China, Gendicine became the
world’s first gene therapy approved for commercial
production. According to newspaper accounts, patients from around the world have been traveling there
to receive this treatment for head and neck squamous
cell carcinoma (HNSCC). The question is how long
will Gendicine remain the world’s only licensed gene
therapy?
Probably, not very long — the Chinese approach is
conceptually identical to one that was developed earlier in the United States but has been moving more
slowly toward licensing — a pace that means gene
therapy will not come into regular use anytime soon.
On the other hand, the number and variety of clinical trials of gene therapy are such that Anderson’s 50year projection could pan out. As of December 2004,
667 human gene transfer clinical protocols had been
submitted for review by the National Institute of
Health’s Recombinant DNA Advisory Committee
(RAC)1 and the U.S. Food and Drug Administration
1
presence of the therapeutic gene in the peripheral
blood cells is negligible.
Anderson went on to collaborate in 12 of the first
20 gene therapy trials approved in the United States. In
an article he wrote about the prospects for gene therapy, he stated, “Indeed, within 20 years, I expect that
gene therapy will be used regularly to ameliorate —
and even cure — many ailments.” More recently, Time
celebrated the 50th anniversary of Watson and Crick’s
Since 1974, the RAC has reviewed technology involving recombinant DNA, including clinical trials involving human gene transfer if direct or indirect NIH funding is provided. Since 1997, the
U.S. Food and Drug Administration has been the principal regulator and overseer of gene therapy trials, while the Recombinant
Advisory DNA Committee has promoted public awareness and
understanding of issues surrounding gene therapy. Yet, the RAC’s
function goes beyond education, taking on powerful and public
scientific, ethics, and policy advisory oversight. The RAC sends
its recommendations to the FDA and local committees, and while
those RAC comments formally are recommendations only, they
carry great influence on the final actions taken by the local review
committees.
PHOTOGRAPH BY ROBERT BURROUGHS
52
BIOTECHNOLOGY HEALTHCARE · JUNE 2005
JUNE 2005 · BIOTECHNOLOGY HEALTHCARE
53
LEADING EDGE
(through its Center for Biologics
Evaluation and Research). Of these,
617 are for therapeutic purposes
(see table on page 56) — as opposed
to marking and nontherapeutic
purposes — but only a handful
have advanced to phase 3. Most are
phase 1 trials whose purpose is to
demonstrate safety. Of the 59 protocols submitted in 2004, the majority originated in academia, but
37 percent had a corporate sponsor (sometimes working in collaboration with a nonprofit group).
MULTITUDE OF TARGETS
With all the hoopla surrounding
the Human Genome Project, it’s
understandable that people would
entertain high hopes for the advancement of gene therapy. The
human genome is now known to
contain some 25,000 genes, including about 22,000 protein-encoding genes that express about
100,000 proteins. But unresolved
questions abound regarding what
these genes and proteins actually
do and how, when, where, and in
what sequence. As answers emerge,
gene therapy could evolve in ways
that will provide numerous benefits
to patients and without deleterious
side effects.
Talking about gene therapy as
though it were a single entity,
though, isn’t very helpful. As explained by David A. Sanders, PhD,
associate professor of biological sciences at Purdue University, gene
therapy falls into three groups:
• Replacing a defective or maladaptive gene that’s responsible for some monogenic disease (e.g., cystic fibrosis or
sickle cell anemia)
• Altering or killing an aberrant
54
cell (e.g., infected by HIV or
cancerous)
• Inducing production of a therapeutic protein (e.g., treating
hepatitis C by promoting secretion of interferon by other
cells)
Initially, gene therapy focused on
the first group, but most current research focuses on the other two.
Whatever the application, numerous hurdles stand in the way of developing a successful gene therapy,
such as:
• Identifying an appropriate target for gene therapy
• Getting a therapeutic transgene into the right cells (and
only those cells) in the right
amount
• Delivering the transgene with
a vector that doesn’t trigger an
immune response or, in the
case of certain viral vectors,
revert to a pathogenic form
• Providing the appropriate regulatory elements for turning
the gene on and off at the correct time
• Keeping the transgene in the
target cell long enough for it to
do its job
• Keeping the transgene from
causing damage elsewhere
(e.g., spurring development of
neoplasms or autoimmune
disease, which could happen
if the transgene expresses a
protein new to the patient’s
body
Aside from the 1,500 or so diseases known to be caused by a single defective gene, most involve
multiple genes, so potential targets
for gene therapy abound. Possible
BIOTECHNOLOGY HEALTHCARE · JUNE 2005
therapies aren’t restricted to the naturally occurring genes and gene
products in the human genome. Fusion genes and nonhuman genes
also are being investigated. An example of a fusion gene is an investigational agent being developed by
Targeted Genetics, based in Seattle,
Wash. This agent fuses the gene for
the Fc fragment of human immunoglobulin G with another gene
for the soluble p75 receptor for
tumor necrosis factor, producing
the same molecule provided by
etanercept (Enbrel). A phase 1 trial
comprising patients who have
rheumatoid arthritis was initiated
in March 2004.
SKY-HIGH EXPECTATIONS
In the view of Theodore Friedmann, MD, who has been deeply
involved in the study of gene therapy for three decades — essentially
its entire modern history — hyperbole surrounding early claims had
the effect of unrealistically heightening expectations that gene therapy would emerge quickly as a
component of health care. Friedmann is a professor of pediatrics at
the University of California–San
Diego, and director of the UCSD
Program in Gene Therapy. A medical ethicist and geneticist, he also
has served on the RAC and was its
chairman until last year.
That the initial human gene
transfer protocol was hailed a success, Friedmann says, is a “perfect
example of the confluence of exaggerated expectations and wishful
thinking. Everyone wanted it to
work.” But, he adds, it was unfair to
patients and the public that the
heightened expectations generated
by some of the scientists and their
institutions, the media, and others
LEADING EDGE
served to raise false hope in many
patients with many kinds of disease.
“Hope is necessary, but knowingly
making undeliverable promises and
raising false hope is cruel,” Friedmann says. “The delusion of a cure
contributed to crashing disappointment later.”
With their early expectations
dashed, people concluded that gene
therapy might be another biotech
bust. Friedmann thinks the perception of failure was also fueled by
widely publicized setbacks being
portrayed as “disasters” — which
he says were regarded as disasters
only because expectations were so
high to start with.
Friedmann sees gene therapy
today at a point comparable to the
early days of organ transplantation,
when successes were scarce and
failures frequent. Even the first clear
success of gene therapy, he notes,
has been muted by the emergence
of three cases of leukemia (including one death) among the 18 children who were treated. The outcome of these cases is that gene
transfer therapy is now reserved for
patients who have had unsuccessful
attempts at bone marrow transplantation or for whom this approach is not feasible.
“These children received very effective treatment, but at a very high
cost,” Friedmann says, “and if additional cases of leukemia develop,
we’ll have a greater problem.” But
he adds, that doesn’t mean that we
should not push ahead with the
field.
WHERE THE PATIENTS ARE
At first it was thought that gene
therapy would focus on monogenic
diseases — hereditary diseases such
as SCID, hemophilia, or cystic fi56
Human gene transfer protocols,
United States and worldwide, 1988-2005
U.S.
total
CANCER
436
Immunotherapy/in vivo transduction
159
Immunotherapy/in vitro transduction
129
Pro-drug/HSV-TK and ganciclovir
45
Tumor suppressor gene
38
Vector-directed cell lysis
28
Other therapeutic approaches
37
60
MONOGENIC DISEASES
Cystic fibrosis
23
Severe combined immunodeficiency
6
(SCID)
Hemophilia
5
Fanconi anemia
4
Other monogenic diseases
22
55
CARDIOVASCULAR DISEASE
Peripheral artery disease
29
Coronary artery disease
21
Other cardiovascular disease
5
42
INFECTIOUS DISEASE
Human immunodeficiency virus
39
Other viral diseases
3
5
CENTRAL NERVOUS SYSTEM DISEASES
(Alzheimer’s disease, Parkinson’s disease,
epilepsy)
19
OTHER DISEASES & DISORDERS
(arthritis, autoimmune disease, bone
fracture, cubital tunnel syndrome,
erectile dysfunction, eye disorders,
intractable pain, peripheral neuropathy,
ulcer)
50
MARKING AND NONTHERAPEUTIC USES
Total gene transfer protocols
667
%
World
total*
%
65
675
66
9
93
9
8
85
8
6
68
7
<1
5
<1
3
26
3
7
68
7
1,020
HSV-TK=herpes simplex thymidine kinase.
* Includes United States.
SOURCES: RECOMBINANT DNA ADVISORY COMMITTEE.
Available at: «http://www4.od.nih.gov/oba/rac/PROTOCOL.pdf»;
GENE THERAPY CLINICAL TRIALS WORLDWIDE.
Available at: «http://www.wiley.co.uk/genmed/clinical».
brosis — that stem from a single
defective gene. The thinking was
that such diseases could be ameliorated, if not cured, by providing the
patient with a properly functioning
gene. Thus far, the initial expecta-
BIOTECHNOLOGY HEALTHCARE · JUNE 2005
tions have not been fulfilled. Moreover, as gene therapy has evolved, it
has drifted away from monogenic
diseases and toward diseases like
cancer.
This makes sense given that can-
PHOTOGRAPH BY SHAWN SPENCE
LEADING EDGE
“Whatever the problems with certain drugs might be, they begin and end in a single generation,” says David A.
Sanders, PhD, associate professor of biological sciences at Purdue University. In contrast, he points out, gene therapy has
the potential to affect a patient for a lifetime, which mandates lifelong observation.
cer is where the patients are and
probably will be. Which is also
where the money will be. According to the American Cancer Society,
cancer has become the leading killer
of Americans under the age of 85,
surpassing cardiovascular disease.
For demographic reasons, it is logical that CVD also would attract the
attention of gene therapy researchers
— and it has, along with incurable
conditions such as Alzheimer’s disease and Parkinson’s disease.
Alameda, Calif.-based Avigen
began a phase 1/2 clinical trial of
AV201 for the treatment of severe
Parkinson’s at the end of 2004. This
agent uses an adeno-associated
virus (AAV) vector to deliver the
gene for an enzyme, acetoacetate de-
carboxylase (AADC), directly into
the striatum. The striatum is the section of the brain where movement is
controlled via dopamine. As Parkinson’s progresses, dopamine levels
decrease. Patients are treated with
levodopa, which is converted to
dopamine by AADC. Eventually, the
effectiveness of levodopa diminishes, presumably because the concentration of AADC declines. The
idea behind AV201 is that with the
enzyme restored, patients once
again will respond to levodopa.
To take another example, some
gene therapy research is exploring
the role of angiogens — molecular
mediators that promote the formation of blood vessels during normal
cardiac and vascular development.
One such angiogen is vascular endothelial growth factor (VEGF). The
VEGF gene consists of eight exons
that can be spliced in different ways
(omitting one or more exons), leading to the synthesis of amino acid
sequences of varying lengths
(specifically, 121, 165, 189, and 206
amino acids). Using an adenovirus
vector, attempts have been made to
transfer cDNA for VEGF121 into
skeletal muscle as a treatment for
peripheral arterial disease and into
myocardial tissue as a treatment for
severe coronary artery disease.
It was once thought that the receptors for the VEGF group of proteins were restricted to endothelial
cells, but they since have been found
in cells of nonendothelial origin, in-
JUNE 2005 · BIOTECHNOLOGY HEALTHCARE
57
LEADING EDGE
cluding tumor cells. That finding
points to a characteristic that gene
therapy shares with pharmacotherapy: the molecular targets of
therapy often are not restricted to
cells in the tissue of interest. That
puts a premium on developing vectors that deliver transgenes to specific cells and only those cells.
teins embedded in the cell membrane determines whether a virus
can enter a given cell. Sanders has
designed a new class of pseudotyped viruses, constructing their
shell from a variety of alphaviruses
and their core from retroviruses and
lentiviruses. Injected into the tail
vein of a mouse, these pseudotyped
viruses are delivered in quantity to
IMPROVING VIRAL VECTORS
the liver. And in the central nervous
Among the numerous vehicles
system, these vectors go specifically
for carrying therapeutic genes to
to glial cells but not to neurons, in
target cells, vectors adapted from
contrast with VSV-G vectors, which
viruses stand out because of
enter neurons but not glial
the ease with which viruses
cells. Sanders says this propThe field of gene therapy is
enter cells and then spill out
erty has important implicadriven largely by medical pro- tions for the treatment of
their contents — the viral
genes that induce the host
fessionals instead of scientists. brain tumors, most of
to generate the components
which are of glial origin.
Because patients are their priof new virions. When a therIn many cases, delivering
apeutic gene is inserted in
a
gene
to the right cells is not
mary concern, doctors might
place of most of the viral
sufficient. The gene also
be predisposed to trying gene must be brought to the corgenome, the virion retains
its ability to penetrate the
rect portion of the cell.
therapy experiments on
target cells while delivering
That’s because many cells
severely ill patients — even if
a presumably beneficial payare polarized, having one
load. The families that have
the science is still a bit ragged. portion of their plasma
been most often used as vecmembrane exposed to the
tors are the adenoviruses and retro- Sanders has been looking at other outside world (the apical memviruses, but AAV and lentivirus are viruses that could be used to create brane) and another exposed to the
among other viral vectors increas- pseudotyped viruses, and he says blood stream (the basolateral memingly employed in gene therapy ex- that he has found alphaviruses to brane). The proteins embedded in
periments. Lentiviruses actually are be promising. Among the species the apical membrane differ from
a genus in the retrovirus family, but in this insect-transmitted genus are those in the basolateral membrane,
they differ from other retroviruses the Ross River virus, Eastern equine and a tight junction prevents proin being able to integrate their encephalitis virus, Semliki Forest teins from passing from one dogenome into the chromosomes of virus, and Venezuelan equine en- main to the other. Because differnondividing cells (e.g., brain, peri- cephalitis virus.
ent proteins offer a foothold for
pheral nerves). Other retroviruses
A protein biochemist by train- different viruses, it’s important to
can transduce only dividing cells.
ing, Sanders did postdoctoral work select a viral vector that’s specific
According to Sanders, one of with Harvard’s Richard Mulligan, for the apical or basolateral memFriedmann’s major contributions, PhD, who joins Friedman as an- brane of polarized target cells, such
among many, to the development other pioneer of gene therapy. as airway epithelial cells in the lung.
of gene therapy was showing that a Sanders is especially interested in Influenza viruses enter and leave
recombinant pseudotyped virus could the proteins found on the exterior these cells through the apical membe created to serve as a vector for de- of viruses, because the way these brane, which is exposed to the outlivering genetic material to cells. proteins match up with other pro- side. But a retrovirus like HIV or
58
The genome of a pseudotyped virus
lacks the coding for one or more of
its structural proteins, which confers a safety benefit and other advantages.
In contemporary gene therapy
experiments, vesicular stomatitis
virus G protein (VSV-G) pseudotyped retroviruses and lentiviruses
are commonly used but have several shortcomings, such as being
toxic to cells producing virus in culture and targeting primary cells in
culture or in vivo. In his own work,
BIOTECHNOLOGY HEALTHCARE · JUNE 2005
LEADING EDGE
murine leukemia would have to
enter through the basolateral membrane, which is exposed to the
bloodstream in which these viruses
find their major target (blood cells).
Sanders explains that a practical
consequence of failure to appreciate the difference between apical
and basolateral membranes is this:
More than a decade ago, the gene
responsible for cystic fibrosis was
discovered. Great excitement ensued, and the success of gene therapy based on this discovery was eagerly anticipated. But success has
been elusive, partly owing to difficulty in getting the therapeutic
gene into the target cells. Sanders
says that’s because researchers used
retroviral vectors that approached
the epithelial cells from the wrong
side (the basolateral side). He says a
more promising approach may be
to base a vector on a modified
Ebola virus shell, which specifically
targets airways epithelial cells and
can enter through the apical membrane if it’s aerosolized. This technique appears to improve gene delivery by two orders of magnitude
compared to retroviral vectors,
Sanders says.
WRONG DRIVER?
Setting aside the specifics of cystic fibrosis, the greater question focuses on why researchers would
use the wrong vector in the first
place. In Sanders’ view, it’s because
the field of gene therapy is driven
largely by medical professionals instead of scientists. The physician’s
paramount concern is to help a patient, and if the patient is severely ill,
the physician may disregard loose
ends or ambiguity in the science
supporting a new technology.
“Medical doctors are interested
First FDA-approved gene therapy
for cancer may be on its way
O
ne frontrunner for the distinction of being the first gene
therapy to win approval from the U.S. Food and Drug
Administration is Advexin, made by Introgen, of Austin,
Texas, and which resembles Gendicine. Both use an adenoviral
vector to deliver the p53 tumor suppressor gene and can be used
in combination with radiotherapy.
Advexin is being studied in two phase 3 trials that are enrolling
patients with recurrent, unresectable head and neck squamous cell
carcinoma. In one trial, Advexin monotherapy is being compared to
methotrexate monotherapy, the primary outcome being the effect
on survival time. The other compares combined chemotherapy plus
Advexin versus the same chemotherapy without Advexin, with the
primary endpoint being the time to progression.
The FDA has designated Advexin as an orphan drug, so if it’s
approved, Advexin could win seven years of marketing exclusivity.
Advexin also is being studied as a treatment for many other cancers.
in the individual patient’s welfare at
all costs,” Sanders says. “I would demand that from my own physician
or a physician for a member of my
family. They are not necessarily the
best evaluators of the societal and
public health effects of their procedures. When confronted with seriously ill patients for whose condition there is no existing effective
treatment they think, ‘Let’s go ahead
and do the experiment anyway.
Maybe it will work.’”
Looking at gene therapy from the
perspective of public health,
Sanders says he’s opposed to doing
gene therapy experiments too early.
“Yes, we did learn some things from
the death of Jesse Gelsinger [the 19year-old who died during a gene
therapy experiment at the University of Pennsylvania in 1999], but
we didn’t have to learn them in that
way,” he says.
As an example of how physicians’ haste to help patients can lead
researchers in the wrong direction,
Sanders cites a key study from
W. French Anderson that paved the
way for the first human gene therapy experiments. With the concern
that a viral vector might acquire the
ability to replicate, it was important
to demonstrate that replication did
not occur if a retrovirus was used as
a vector. Toward this end, Anderson and colleagues injected rhesus
macaques (a proxy for human subjects) with a replication-competent
murine leukemia retrovirus. Because no infection developed in the
macaques, the researchers concluded that murine retrovirus probably would not pose an acute health
risk in humans. The researchers attributed the lack of infection in the
monkeys to neutralization of the
retrovirus by complement.
Nonetheless, there was a problem, Sanders says. The presence of
complement implies the presence
of antibodies against the retrovirus.
The question of where those antibodies came from should have
JUNE 2005 · BIOTECHNOLOGY HEALTHCARE
59
LEADING EDGE
given the researchers pause. When crops. As he sees it, the major issue who have received gene therapy be
another team of researchers did a with transgenic plants isn’t their po- allowed to donate blood? Probably
similar experiment at a later date, tential to affect human health, as not, in Sanders’s opinion, given
they used a recombinant retroviral many critics fear, but rather the pos- how little we know at this point
vector that was contaminated with sibility that genes introduced into about long-term outcomes in gene
a replication-competent virus. And, crops in the hope of improving agri- therapy. Then there’s the important
whereas in the first experiment the culture might find their way into political question of whether the
virus was introduced in vivo, in the other plants with detrimental re- contemporary pharmaceutical insecond the virus was mixed with sults for the whole environment. He dustry should serve as the model
cells in culture, and the cells were thinks similar ecological issues for the development of gene therreintroduced into the monapy. Sanders observes that
keys. This time, the monIf society supports widespread the big money generated by
keys developed leukemia.
small molecules and biologgene therapy directed at dis“There was a huge
ics is for treating chronic disamount of retroviral repliease prevention — in addition eases, not for preventing discation,” Sanders says. The
ease. If society supports
to treating existing disease — widespread gene therapy diresults differed, he explains,
because mice and most
rected at disease prevention
Sanders wonders, who will
other mammals possess a
in addition to treating existdetermine
how
and
what
sugar, galactose-alpha (1,3)ing disease, who will detergalactose, as a component
resources should be allocated mine how and what reof glycoproteins on cell sursources should be allocated
toward that end?
faces, but Old World montoward that end?
keys (and humans, along
Given the genetic basis
with the great apes) lack this sugar. apply to gene therapy. If someone for most diseases, instead of conYet, they have ample antibodies receives a treatment with a recom- templating the future of gene theragainst it — from 1 to 3 percent — binant virus that has the potential to apy, it might be equally interesting
because alpha-galactose is found on replicate, can untreated individuals to wonder about the future of gene
the coat of many viruses that infect also be receiving gene therapy? And therapy in the context of drug therthese animals. When the antibodies if DNA enters the germ line as a re- apy. Right now, whether the disease
recognize a virus sporting this sult of gene therapy, the effects is cancer or CVD, gene therapy insugar, the complement cascade is could be felt by future generations. vestigations for the most part are
triggered. That’s what happened in
The societal implications of gene focused on developing new treatthe first experiment, creating the il- therapy are so profound that a cau- ments for high-risk patients with
lusion of safety. In the second ex- tious, step-by-step approach is war- severe illness — patients beyond the
periment, with the transduction ranted, Sanders says. “Gene therapy point where conventional treattaking place in a cell culture instead will become a component of 21st ment is effective. Eventually, howof in vivo, there was no possibility of century medicine. There’s no rea- ever, conventional treatments and
an immune response. As a result, son it can’t work. But huge ques- gene therapies will overlap. Thorny
the viruses produced in culture tions remain to be resolved. The his- ethical and political issues will have
lacked the sugar and went unde- tory of mankind tells us that to be addressed, but, over the long
tected and replicated, causing leu- whenever you have new technol- term, the future of drug therapy
kemia when the cells were returned ogy, you have problems. But by now could be gene therapy.
BH
to the macaques.
we should be intelligent enough to
anticipate the problems that might Based in Durham, Conn., Jack McCain is
a freelance medical writer and editor. He
ECOLOGY OF GENE THERAPY
be associated with gene therapy.”
Sanders likens gene therapy to
What are some of these prob- holds degrees from Allegheny College and
the development of transgenic lems? For starters, should patients Wesleyan University.
60
BIOTECHNOLOGY HEALTHCARE · JUNE 2005