Genetic Enhancement
In general, genetic enhancement refers to the transfer of genetic
material intended to modify nonpathological human traits. The term
commonly is used to describe efforts to make someone not just well, but
better than well, by optimizing attributes or capabilities -- perhaps by
raising an individual from standard to peak levels of performance. When
the goal is enhancement, the gene may supplement the functioning of
normal genes or may be superseded with genes that have been engineered
to produce a desired enhancement. Furthermore, gene insertion may be
intended to affect a single individual through somatic cell
modification, or it may target the gametes, in which case the resulting
effect could be passed on to succeeding generations.
In a sense, the concept of genetic enhancement is not particularly
recent if one considers genetically engineered drug products used to
alter physical traits as genetic enhancements. For example, human growth
hormone (HGH), which before 1985 could be obtained only in limited
quantities from cadaveric pituitary glands, now can be produced using
recombinant DNA technology. When its supply was more limited, HGH was
prescribed for children with short stature caused by classical growth
hormone deficiency. However, with the advent of recombinant DNA
manufacturing, some physicians have begun recommending use of HGH for
nonhormone-deficient children who are below normal height.
Animal Models and Possibilities for Human Application
Animal experiments to date have attempted to improve such traits as
growth rate or muscle mass. Although this research is focused on
developing approaches to treating human diseases and conditions, it is
conceivable that developments resulting from this research could be more
broadly applied to enhance traits rather than correct deficiencies.
Recently, Schwarzenegger mice have been bred - laboratory
animals whose bodies have expanded rapidly after the injection of a gene
that causes muscles to grow. The mice are the first stage in the
development of treatments intended to coax the bodies of seriously ill
patients with degenerating diseases to recreate damaged tissue (e.g.,
muscular dystrophy). In the world of sports, this technology could
potentially be used to improve athletic performance without being
detected.
Similar interventions could help delay the aging process. For
example, a gene called MGF (Mechano-growth factor) regulates a naturally
occurring hormone produced after exercise that stimulates muscle
production. Levels of MGF fall as we age, which is one reason why muscle
mass is lost as we grow older. A treatment to build up muscles would
allow us to remain able-bodied and independent much longer. IGF-1,
another muscle-building hormone, has produced increased muscle mass in
laboratory mice. Theoretically, gene insertion of IGF-1 could produce an
equally impressive effect in humans.
Efforts to genetically improve the growth of swine have involved the
insertion of transgenes encoding growth hormone. Nevertheless, despite
the fact that growth hormone transgenes are expressed well in swine,
increased growth does not occur. Another effort aimed to enhance muscle
mass in cattle. When gene transfer was accomplished, the transgenic calf
initially exhibited muscle hypertrophy, but muscle degeneration and
wasting soon followed and the animal had to be destroyed.
Gene transfer at the embryonic stage through a technique called
pronuclear microinjection is another approach being tested in animals.
However, current knowledge from animal experiments suggests that embryo
gene transfer is unsafe, as its use results in random integration of
donor DNA, a lack of control of the number of gene copies inserted,
significant rearrangements of host genetic material, and a 5 to 10
percent frequency of insertional mutagenesis. In addition, this
technique would necessarily be followed by nuclear transfer into
enucleated oocytes, a process that in at least two animal models is
associated with a low birth rate and a very high rate of late pregnancy
loss or newborn death. Thus, many believe that the use of gene transfer
at the embryonic stage for enhancement would reach far beyond the limits
of acceptable medical intervention.
Greater success has been achieved in genetic enhancement of plants,
which are more easily manipulated genetically and reproductively.
However, the state of knowledge in humans and other complex organisms
does not allow for the controlled genetic modification of even simple
phenotypes.
For example, in humans, for whom more complex traits such as
intelligence or behavior are concerned, the limitations are more
pronounced. The genome provides only a blueprint for formation of the
brain. The complex and subtle details of assembly and intellectual
development involve more than direct genetic control and are subject to
inestimable stochastic and environmental influences. Despite the
technical limitations, it is possible that eventually enhancements using
techniques initially intended to restore deficiencies could be
redirected to improve memory and problem-solving, reduce the need for
sleep, increase musical capacity, attain desirable personality traits,
protect against cardiovascular disease or cancer, or increase longevity.
One of the areas in which genetic enhancement might find initial
application is in sports. At the 1964 Winter Olympics in Innsbruck, a
cross-country skier from Finland who won two gold medals was later found
to have a genetic mutation that increased the number of red blood cells
in his body because he could not switch off erythropoetin (Epo)
production. This mutation increased the athlete's capacity for aerobic
exercise. A synthetic version of Epo is currently used to treat anemia,
but it has also been abused by athletes to heighten their stamina. For
example, in the 1998 Tour de France, a team was thrown out of the race,
and two top cyclists admitted taking the drug. Recent efforts to deliver
the Epo gene into patients' cells would eliminate the need for regular
injections, but this process could also be abused by athletes.
Ethical Concerns
Genetic enhancement raises a host of ethical, legal and social
questions. What is meant by normal? When is a genetic intervention
"enhancing" or "therapeutic?" How should the benefit from a genetic
enhancement be calculated in comparing its risks and benefits? Would
people who have been genetically enhanced enjoy an unfair advantage in
competing for scarce resources? That is, will genetic enhancement be
available to all or only to the few who can afford to purchase it using
their personal finances? These questions relate to the two major
concerns presented by genetic enhancement: the undermining of the
principle of social equality and the problem of creating an unfair
advantage that would be enjoyed by enhanced individuals.
Some have speculated that genetic enhancement might affect human
evolution. Philosophical and religious objections also have been raised,
based on the belief that to intervene in such fundamental biological
processes is "playing God" or attempting to place us above God. People
from various perspectives believe that any interference with the random
offerings of nature is inherently wrong and question our right to toy
with the product of years of natural selection. Geneticists have
countered that the power to control human evolution is unlikely, as the
evolution of the human species is a nonrandom change in allelic
frequencies resulting from selective pressure. The change progresses
over generations because individuals with specific patterns of alleles
are favored reproductively. If new alleles were introduced by gene
transfer, the impact on the species would be negligible. Moreover, there
is no certainty that genetically enhanced individuals would have
greater biological fitness, as measured by reproductive success.
In general, however, ethical and social concerns center not so much
on the improvement of traits for alleviation of deficiencies or on the
reduction of disease risk, but on the augmentation of functions that
without intervention would be considered entirely normal. For some
individuals, technologies that can enhance traits are even more
attractive than those that would merely duplicate them (e.g., cloning).
And, although the distinctions between cure and enhancement might be
obvious to some, they can lose meaning in medical practice or in
formulating health policy. For example, interventions that begin in an
effort to cure could slide quickly toward interventions that enhance.
Regulatory Issues
The questions raised above also create significant new challenges to our regulatory capabilities.
On September 11, 1997, the National Institutes of Health (NIH)
convened a conference on genetic enhancement. The meeting was prompted
by a request to NIH to approve a protocol for conducting a gene therapy
experiment on healthy volunteers, rather than on patients. Although the
experiment was part of an effort to develop treatments for cystic
fibrosis, the proposed use of healthy subjects raised, for the first
time, the questions of whether and in what circumstances it was
appropriate to use gene insertion technology in healthy volunteers.
Exactly how to regulate this potential use of genetic technology remains
unclear.
In order for the Food and Drug Administration (FDA) to control the
introduction and use of genetic enhancement technologies, these
techniques would have to be considered to be drugs, biologics, or
medical devices, categories for which FDA has the authority to regulate
genetic enhancements. Regarding drugs used for enhancement purposes, the
definition of a drug in the Federal Food, Drug, and Cosmetic Act
includes not only "articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man" but also
"articles (other than food) intended to affect the structure or function
of the body of man." The agency has relied on this definition to assert
drug regulatory authority over products such as wrinkle creams and
tanning agents that are intended to enhance the appearance of the body
but that achieve results by affecting the body's structural or
functional components. The agency will be challenged by the need to
determine when enhancement is "genetic" (versus nongenetic, for example,
liposuction or cosmetic surgery) and when genetic manipulation is
"enhancement." In addition, FDA's ability to regulate genetic
enhancements in the traditional areas of safety and efficacy will be put
to the test by data deficiencies and the subjectivity of judgments
about risk and benefit. In addition, enhancement techniques are likely
to emerge as unapproved or off-label uses of approved products, uses
over which FDA lacks effective regulatory control.
