G athered around an enclosure at the Wake Forest
Institute for Regenerative Medicine in North
Carolina in 2008, Anthony Atala and his
colleagues watched anxiously to see if two rabbits
would have sex. The suspense was short-lived: within
a minute of being put together, the male mounted the
female and successfully mated.

While it’s not clear what the rabbits made of the
moment, for Atala it was definitely special. It was
proof that a concept he’d been working on since 1992 –
that joysticks could be grown in a laboratory and
transplanted to humans – was theoretically possible.
The male rabbit was one of 12 for which he had
bioengineered a penis; all tried to mate; in eight there
was proof of ejaculation; four went on to produce
offspring.

The media’s coverage of Atala’s announcement a year
later was understandably excited. Not just because of
the novelty of a man growing joysticks in a laboratory,
but because his work would fulfil a real need for men
who have lost their penis through genital defects,
traumatic injury, surgery for aggressive penile cancer,
or even jilted lovers exacting revenge.

At present, the only treatment option for these men is
to have a penis constructed with skin and muscle from
their thigh or forearm. Sexual function can be
restored with a penile prosthetic placed inside. The
prosthetics can be either malleable rods, with the
penis left in a permanently semi-rigid state and thus
difficult to conceal, or inflatable rods, which have a
saline pump housed in the scrotum. Both technologies
have been around since the 1970s. The aesthetics are
crude and penetration is awkward.

Another option is a penis transplant from another
individual, but this carries a risk of immunological
rejection. The chance of organ death can be lessened
with anti-rejection drugs, but these drugs have serious
side-effects. Transplants can also have a psychological
impact, especially with an organ as intimate as the
penis. In 2006, a Chinese man was the first to receive a
donor penis; two weeks after the 15-hour operation,
surgeons removed the transplanted organ on the
request of both the patient and his partner.
Atala hopes his technique will mitigate both
immunological and psychological issues because his
joysticks would be engineered using a patient’s own
cells. “The phallus is actually much longer than you
think,” he explains. “It goes all the way behind the
pelvis, so no matter the extent of the damage, there is
a high probability that there are salvageable cells.”
Peruvian-born Atala, a urological surgeon and
professor of regenerative medicine, heads a 300-strong
team at the institute. He corrects himself constantly,
always going back to edit his speech, adding words
such as “high probability“ or “in all likelihood” to be
sure his sentences are word-perfect. Soft-spoken and
mild-mannered, Atala is a trailblazer in the field and
you can’t help but think that his measured speech is
an attempt to provide a sure path for others to follow.
To some, engineering human organs sounds like
science fiction, but for Atala it’s an absolute necessity.

As we live longer (and thus our organs fail more) the
shortage of organs for donation will only get worse. If
he can work out how to generate the organs people
need in a reliable and effective way, the technology
can improve a lot of people’s lives. In 2006, Atala and
his team announced the first successful bioengineered
organ transplant, a bladder, which had been implanted
into seven patients in 1999. Earlier this year he
announced the successful follow-up of four women
given bioengineered vaginas in 2005-2008. Despite
these successes, he says, the penis is proving trickier.
Organs increase in architectural complexity as they go
from flat structures such as skin, cylindrical structures
such as the vagina, to hollow non-tubular organs such
as the bladder. As a solid organ, the penis tops this list
in both density of cells and structural complexity. It
consists of a spongy erectile tissue unique to it.

During an erection, signals from the nerves trigger
blood vessels to dilate, filling this spongy tissue with
blood and causing the penis to lengthen and stiffen.
“We were completely stuck,” says Atala of the first few
years of research in the early 90s. “Even the idea of
the field of regenerative medicine was brand new at
the time. We had no idea how to make this structure,
let alone make it so it would perform like the natural
organ.” Then, in 1994, he figured he could take a
helping hand from Mother Nature. Using a technique
pioneered for biological skin dressings, he would take
a donor penis and soak it in a mild detergent of
enzymes for a couple of weeks to wash away the
donor cells.
“You’re left with a mostly collagen scaffold – a skeleton
if you like, that looks and feels just like the organ,”
explains James Yoo, one of Atala’s collaborators at the
institute. “Think of it like a building. If you remove all
the furniture and the people, you’re still left with the
main structure of the building. Then you replace the
tenants with new ones. That’s the whole idea. It’s just
that the building is a penis and the tenants are cells.”

The next step is to reseed the structure with the
patient’s own cells taken in a biopsy from salvageable
tissue and grown in culture. Smooth muscle cells,
which relax during an erection to allow the vessels to
dilate and the penis to fill with blood, are first,
followed by endothelial cells which line the interior
surface of blood and lymphatic vessels. When ready,
the bioengineered penis is ready to be transplanted to
the recipient.

So why, six years on from successfully engineering a
penis for rabbits, have they not yet done the same for
humans? Atala explains that, as is often the case with
these things, scaling up is proving difficult. “Even
though we can make them in a very small mammal,
we have to tweak the technology, the processes, the
ratio of cells and so on, to get larger and larger
structures. That’s pretty much what we’ve been doing
since the rabbits.”

They’ve made encouraging progress. Atala has
engineered half a dozen human joysticks. Although they
are not yet ready for transplanting, Atala’s team are
assessing the structures for safety and effectiveness.
One machine squashes, stretches and twists them to
make sure they can stand up to the wear of everyday
life; another pumps fluid into them to test erections.
Sliced segments are tested at the genetic, cellular and
physiological level.

“It’s a rigorous testing schedule,” says Atala, wearily.
“But we’re trying to get approval from the US Food
and Drug Administration so we know everything is
perfect before we move to a first in-man test.”
Neither Atala nor Yoo will be pushed for a date for the
first test in man, saying only that they’d expect it to
occur within five years. “In the end we’re aiming for
the entire size of the organ,” says Atala. “But in
reality our first target is going to be partial
replacement of the organ.”

In the short term, this would include growing smaller
lengths for partially damaged joysticks, but would also
include replacing parts of the penis to help cure
erectile dysfunction. Degradation of the spongy
erectile tissue, says Tom Lue, a urological surgeon at
the University of California, San Francisco, is the
leading cause of impotence in old age. Disorders such
as high blood pressure or diabetes can damage the
delicate tissue – the resulting scar tissue is less elastic,
meaning the tissue cannot completely fill with blood
and the penis cannot become fully erect.
“
Show me a hundred 70-year-old men with erectile
dysfunction,” says Lue, “and I’ll bet you 90% of them
have scar material in their penis.” Traumatic injury or
priapism, a condition that leaves men with an
increasingly painful erection for hours or even days,
can also damage the tissue and cause erectile
dysfunction in younger men. “If you replace the
damaged spongy tissue you can give these men a
better erection.”

Engineering the spongy tissue for replacement is one
of Atala and Yoo’s interim goals. Lue is also hoping to
restore erections, but for less severely damaged
joysticks. For instance, some men become impotent
after surgery for prostate or rectal cancer because the
nerves that regulate erections, which run through the
rectum and prostate into the centre of the penis, can
get damaged. Likewise with traumatic injury, if the
vessels are severed then the penis cannot fill with
blood.

Microsurgery to connect the vessels and nerves in the
penis is possible but often ineffective. Lue is testing
whether injecting stem cells into the base of the penis
can encourage the nerves and cells to rejoin. His work
might also help Atala and Yoo to stimulate nerve and
vessel regrowth when the day comes for the first in-
man trial of a bioengineered penis. Twenty-two years
into his research to bioengineer a human penis, Atala
is a man who is both excited and impatient for that
day. And you’d suspect he’s not the only one.

source:
http://www.theguardian.com/education/2014/oct/04/penis-transplants-anthony-atala-interview

Soon there will be no more Sadstick! Lol