The new frontier of doping will modify athletes' DNA
The new frontier of doping will modify athletes' DNA
Story highlights
In the 1990s Lee Sweeney made headlines with his
'schwarzenegger mice'
He soon received calls from multiple athletes in hope of
a genetic performance boost
In 2008, an Olympic year, Lee Sweeney's phone was ringing
nonstop.
By Nick Busca, CNN Updated 4:04 AM ET, Fri April 13, 2018
For a busy physiologist at the University of
Pennsylvania's Perelman School of Medicine, that may be expected, but the
reason behind the calls wasn't exactly run-of-the-mill.
The people on the other end of the line were athletes in
search of a particular kind of fix: They wanted him to dope them -- via their
genes.
In the late 1990s, Sweeney made headlines because of his
research on "Schwarzenegger mice," which were up to 30% stronger than
their average counterparts. Sweeney had been able to isolate the gene
responsible for activating a protein -- IGF-1 -- that controls muscle growth
and repair.
The main focus of his experiments was on how to limit the
deterioration of muscles with age, but the results also appealed to athletes in
search of a performance boost.
Word got out, however, that he was not interested.
Ahead of this year's Commonwealth Games, which started
April 4, Sweeney's was not such a hot number for athletes in search of an
unfair advantage -- possibly because he is now an adviser for the World
Anti-Doping Agency.
"At the beginning, when we first started publishing
on this, we did get contacted by high-level athletes," said Sweeney, who's
also director of the University of Florida's Myology Institute. "These
days, it's mostly body builders and people desperate to increase their
performance or abilities."
Back then, gene therapy -- defined as the technique of
using and manipulating genes in order to treat or prevent diseases -- wasn't as
established as it is today and wasn't recognised as enough of a threat to be
listed as a banned practice in sport. But it soon became known that gene
therapies could one day be used for much more than disease.
Responding promptly to the possibility, in 2002, the
anti-doping agency established "gene and cell-doping panels" of
expert scientists to discuss how best to head off the problem.
In 2003, the organization banned "gene doping,"
which it defined as the "nontherapeutic use of cells, genes, genetic
elements, or modulation of gene expression, having the capacity to enhance
performance."
This new frontier of doping presented a simple and dark
idea: What if there was a way for dopers to never be caught?
Now, almost 20 years later, the technology is has finally
been used to treat patients with rare diseases -- such as severe combined
immunodeficiency, chronic granulomatous disorder, hemophilia, blindness, cancer
and neurodegenerative diseases -- by transferring missing genes into skeletal
muscles, Sweeney said. "So because of that, it is now at a point where
potentially it could be used by athletes.
"It could be done today in athletes if some company
and government would put the resources (in) to make it happen," he said.
Getting inside your genes
In the case of the "Schwarzenegger mice,"
Sweeney used the classic method of gene therapy, in which he modified the
animals' DNA using a virus to deliver and insert the required gene that would
make the mice stronger.
Genes are delivered into an organism using a
"vector," the most common being viruses, like that used by Sweeney,
which have been modified to be safe and no longer cause disease. The vectors
carry the desired gene into targeted cells and, there, unload the genetic
material, which in turn instructs the organism to produce the protein the gene
encodes.
One example of a protein well-known to athletes is
erythropoietin, commonly known as EPO, which regulates the production of red
blood cells in the body, increasing hemoglobin and oxygen delivery to tissues.
With the injection of external EPO, elite athletes --
often cyclists -- have been enhancing performance for years, but authorities
have caught on. Anti-doping controls can now detect external EPO efficiently
through blood and urine tests.
If extra EPO is being produced organically by a cell's
machinery, however, it is almost impossible to detect as a banned substance.
But the technology is not quite at that level yet.
"Making the viruses that are involved in doing the
gene transfer is still difficult," Sweeney said, highlighting that the
science is still complicated and not something athletes could readily do at
home.
Another way to dope an athlete's genes is through CRISPR,
or CRISPR-Cas9, a technique that allows geneticists to edit specific parts of a
person's genome by removing or altering sections of DNA -- also known as gene
editing.
The technique is rapidly developing, leading to a World
Anti-Doping Agency announcement in October that it was expanding its
"gene-doping" ban to "gene editing agents designed to alter
genome sequences and/or the transcriptional or epigenetic regulation of gene
expression."
The ban went into effect in January.
"There's a couple of ways you can use
CRISPR-Cas9," Sweeney said. "One is to take cells from a person,
modify those cells and put them back into the person, and that is probably the
safest way to use it.
"The other way to use it, which is to modify your
existent DNA in the body, is potentially very unsafe."
Sweeney pointed out that scientists do not know what
unintended consequences could come from changing a specific gene in an
individual, meaning the technology is not even ready for trials in patients
with lethal diseases.
In the case of gene-doping through gene therapies, using
vectors for delivery, it's relatively easy to look for an extra copy of a gene
and confirm that an athlete has been doped when you have access to a biological
sample, such as blood, said Olivier Rabin, senior executive director of
sciences and international partnerships at the anti-doping agency.
In particular, Rabin said, the agency looks at
white-blood cells and has developed a methodology that can be applied to search
for different genes. Further detail was not provided, as it is kept
confidential in order to catch athletes, he added.
"Gene editing is a little more complex than gene
therapy," Rabin added. The anti-doping agency is working on strategies to
reveal the possibility of people editing their genes for performance
enhancement, he said.
Rabin highlighted that most of the agency's efforts focus
on white blood cells as "pretty good markers of gene manipulation"
because some evidence of manipulation will usually end up in the blood.
Asked what it is doing to monitor and test athletes for
gene doping, the International Olympic Committee did not comment directly but
said, "We have nothing to add to the section on gene doping in WADA's
prohibited list."
The question now is whether the first few cases have, in
fact, happened without our knowledge.
Modern occurrence
"I never heard anything about it except for one
time, and it was around five years ago," said Sebastian Weber, coach of
four-time Union Cycliste
Internationale world champion (time trialling) Tony
Martin. "There was some buzz around a substance called AICAR," or
5-Aminoimidazole-4-carboxamide ribonucleotide.
AICAR is a performance-enhancing drug that the French
Anti-Doping Agency suspected was used in the 2009 Tour de France; it stimulates
mitochondria, the part in the muscles responsible for aerobic energy
production.
In cycling, for gene doping to be effective, techniques
should target both EPO levels and red blood cell production to have a higher
oxygen delivery to the muscles, Weber says -- but they would also need to
increase the mass and number of mitochondria in order to actually produce
energy from that oxygen.
"Just because you have more oxygen, it doesn't
necessary mean you also have the capacity to produce energy out of it,"
Weber said.
As AICAR was a drug, it wasn't gene doping, but it led
people to wonder about what was next, he says, after this "first
step" toward stimulating the body's mitochondria. "That was the only
time I heard people talking about the possibility of gene-doping."
Tailoring to your genes
There are other ways genetics -- and a deep knowledge of
them -- could help athletes improve their performance, by understanding their
physiology.
For example, project GENESIS -- focused on how applied
genomics in elite sports can improve performance -- and its offshoot, the
RugbyGene Project, are trying to identify which genetic characteristics help
athletes succeed.
"We recognize it is not only genetic," said Dr.
Alun Williams, an exercise geneticist at Manchester Metropolitan University in
the UK who works on both projects. "Training, diet and other lifestyle
habits are massive factors. But along with that, the evidence is that it's
impossible to have success in sports without some genetic [factors] in your
favor."
The researchers of these projects are hoping to identify
which genes help -- or hinder -- athletes in their specific disciplines, to
develop their skills in a more tailored way. For example, if an athlete has
shown to have a higher genetic vulnerability to tendon injuries, scientists and
coaches could reduce certain aspects of their training load over the course of
the season, give longer rest periods, reduce the number of matches played in a
season, or provide specific exercises and pre-habilitation workouts.
But Williams points out that the field is still at an
early stage. "This picture where certain genes (or even two or three
genes) are related to a particular characteristic, like the tendon injury, is
still a small bit of a bigger picture," he said. "So it's very
important that this information that is available is put into context."
A different point of view
Some experts argue that we're looking at it all wrong and
that athletes will always use the most modern technology to seek out an
advantage -- illegal or not.
"Modern sports have been principally valued on the
basis of record-breaking and being able to witness extraordinary
performances," said bioethicist Andy Miah, the University of Salford Chair
in Science Communication and Future Media and author of "Genetically
Modified Athletes: Biomedical Ethics, Gene Doping and Sport." "Even
if it's not a world record, it's about trying to see something special in what
humans can do, and often, that is about transcending boundaries."
We give athletes all sort of technology to do that, added
Miah, who readily claims to "disagree with anti-doping."
Instead of the current scenario, in which anti-doping
keeps trying to catch up with doping, Miah suggests a safer form of performance
enhancement.
"If we can have a system where enhancement was
actually medically supervised, then I think that is a much more safe and
healthy.
Nick Busca is a triathlon coach, personal trainer and CNN
sport and health contributor.
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