Thanks to the remarkable evolution of organ transplantation, it's now possible to replace genitals that don't work properly or have been injured. Surgeons have been transplanting ovarian tissue for more than a decade, and they're now successfully transplanting penises and wombs too.
Rules and regulations aren't keeping up with the rapid rise of genital transplants.
Earlier this year, an American soldier whose genitals were injured by a bomb in Afghanistan received the first-ever transplant of a penis and scrotum at Johns Hopkins Medicine.
Rules and regulations aren't keeping up with the rapid rise of genital transplants, however, and there's no consensus about how society should handle a long list of difficult and delicate questions.
Are these expensive transplants worth the risk when other alternatives exist? Should men, famously obsessed with their penises, be able to ask for a better model simply because they want one? And what happens when transplant technology further muddles the concept of biological parenthood?
"We need to remember that the human body is not a machine with interchangeable parts," says bioethicist Craig M. Klugman of DePaul University. "These are complicated, difficult and potentially dangerous surgeries. And they require deep consideration on a physical, psychological, spiritual, and financial level."
From Extra Testicles to Replacement Penises
Tinkering with human genitalia -- especially the male variety -- is hardly a new phenomenon. A French surgeon created artificial penises for injured soldiers in the 16th century. And a bizarre implant craze swept the U.S. in the 1930s when a quack physician convinced men that, quite literally, the more testicles the merrier – and if the human variety wasn't available, then ones from goats would have to do.
Now we're more sophisticated. Modern genital transplants are designed to do two things: Treat infertility (in women) and restore the appearance and function of genitals (in men).
In women, surgeons have successfully transplanted ovarian tissue from one woman to another since the mid-2000s, when an Alabama woman gave birth after getting a transplant from her identical twin sister. Last year, for the first time in the U.S., a young woman gave birth after getting a uterus transplant from a living donor.
"Where do you draw the line? Is pregnancy a privilege? Is it a right?"
As for men, surgeons in the U.S. and South Africa have successfully transplanted penises from dead men into four men whose genitals were injured by a botched circumcision, penile cancer or a wartime injury. One man reportedly fathered a child after the procedure.
The Johns Hopkins procedure was the first to include a scrotum. Testicles, however, were not transplanted due to ethical concerns. Surgeons have successfully transplanted testicles from man-to-man in the past, but this procedure isn't performed because the testes would produce sperm with the donor's DNA. As a result, the recipient could father a baby who is genetically related to the donor.
Are Transplants Worth the Expense and Risk?
Genital transplants are not simple procedures. They're extremely expensive, with a uterus transplant estimated to cost as much as $250,000. They're dangerous, since patients typically must take powerful drugs to keep their immune systems from rejecting their new organs. And they're not medically necessary. All have alternatives that are much less risky and costly.
Dr. Hiten D. Patel, a urologist at Johns Hopkins University, believes these types of factors make penis transplants unnecessary. As he wrote in a 2018 commentary in the journal European Urology, "What in the world are we doing?"
There are similar questions about female genital transplants, which allow infertile women to become pregnant instead of turning to alternatives like adoption or surrogacy. "This is not a life-saving transplant. A woman can very well live without a uterus," says McGill University's Dr. Jacques Balayla, who studies uterine transplantation. "Where do you draw the line? Is pregnancy a privilege? Is it a right? You don't want to cause harm to an individual unless there's an absolute need for the procedure."
But Johns Hopkins urologist Dr. Arthur L. Burnett II, who served on the surgical team that performed the penis-and-scrotum procedure, says penis transplants can be appropriate when other alternatives – like a "neophallus" created from forearm skin and tissue – aren't feasible.
It's also important to "restore normalcy," he says. "We want someone to be able to have sense of male adequacy and a normal sense of bodily well-being on both physical and psychological levels."
Surgical team members who performed the penis transplant, including W. P. Andrew Lee, director of the department of plastic and reconstructive surgery, center.
As for the anonymous recipient, he's reportedly doing "very well" five months after the transplant. An update on Johns Hopkins' website states that "he has normal urinary functions and is beginning to regain sensation in the transplanted tissues."
When the Organ Donors Do It Live
Some peculiar messages reached Burnett's desk after his institution announced it would begin performing penis transplants. Several men wanted to donate their own organs. But for now, transplanted penises are only coming from dead donors whose next of kin have approved the donation.
Burnett doesn't expect live donors to enter the penis transplant picture. But there are no guidelines or policies to stop surgeons from transplanting a penis from a live donor or, for that matter, a testicle.
Live women have already donated wombs and ovarian tissue, forcing them to face their own risks from transplant surgery. "You're putting the donor at risk because she has to undergo pretty expensive surgery for a procedure that is not technically lifesaving," McGill University's Balayla says.
When it comes to uterus transplants, the risk spreads even beyond donor and recipient. Balayla notes there's a third person in the equation: The fetus. "Immunosuppressant medication may harm the baby, and you're feeding the baby with a [uterine] blood vessel that's not natural, held together by stitches," he says.
It's up to each medical institution that performs the procedures to set its own policies.
Bioethicists are talking about other issues raised by genital transplants: How should operations for transgender people fit in? Should men be able to get penis transplants for purely cosmetic reasons? And then there's the looming question of genetic parenthood.
It's up to each medical institution that performs the procedures to set its own policies.
Let's say a woman gets a transplant of ovarian tissue, a man gets a testicle transplant, and they have a baby the old-fashioned way.* The child would be genetically linked to the donors, not the parents who conceived him or her.
Call this a full-employment act not just for bioethicists but theologians too. "Catholicism is generally against reproductive technologies because it removes God from the nature of the procreative act. This technology, though, could result in conception through the natural act. Would their concern remain?" DePaul University's Klugman asked. "Judaism is concerned with knowing a child's parentage, would a child from transplanted testes be the child of the donor or the recipient? Would an act of coitus with a transplanted penis be adultery?"
Yikes. Maybe it's time for the medical field or the law to step in to determine what genital transplants surgeons can and can't -- or shouldn't -- do.
So far, however, only uterus transplants have guidelines in place. Otherwise, it's up to each medical institution that performs the procedures to set its own policies.
"I don't know if the medical establishment is in the position to do the best job of self-regulation," says Lisa Campo-Engelstein, a bioethicist with Albany Medical College. "Reproductive medicine in this country is a huge for-profit industry. There's a possibility of exploitation if we leave this to for-profit fertility companies."
And, as bioethicist Klugman notes, guidelines "aren't laws, and people can and do violate them with no effect."
He doesn't think laws are the solution to the ethical issues raised by genital transplants either. Still, he says, "we do need a national conversation on these topics to help provide guidance for doctors and patients."
[Correction: The following sentence has been updated: "Let's say a woman gets a transplant of ovarian tissue, a man gets a testicle transplant, and they have a baby the old-fashioned way." The original sentence mistakenly read "uterus transplant" instead of "ovarian tissue."]
In late March, just as the COVID-19 pandemic was ramping up in the United States, David Fajgenbaum, a physician-scientist at the University of Pennsylvania, devised a 10-day challenge for his lab: they would sift through 1,000 recently published scientific papers documenting cases of the deadly virus from around the world, pluck out the names of any drugs used in an attempt to cure patients, and track the treatments and their outcomes in a database.
Before late 2019, no one had ever had to treat this exact disease before, which meant all treatments would be trial and error. Fajgenbaum, a pioneering researcher in the field of drug repurposing—which prioritizes finding novel uses for existing drugs, rather than arduously and expensively developing new ones for each new disease—knew that physicians around the world would be embarking on an experimental journey, the scale of which would be unprecedented. His intention was to briefly document the early days of this potentially illuminating free-for-all, as a sidebar to his primary field of research on a group of lymph node disorders called Castleman disease. But now, 11 months and 29,000 scientific papers later, he and his team of 22 are still going strong.
On a Personal Mission<p>In the science and medical world, Fajgenbaum lives a dual existence: he is both researcher and subject, physician and patient. In July 2010, when he was a healthy and physically fit 25-year-old finishing medical school, he began living through what would become a recurring, unprovoked, and overzealous immune response that repeatedly almost killed him.</p><p>His lymph nodes were inflamed; his liver, kidneys, and bone marrow were faltering; and he was dead tired all the time. At first his doctors mistook his mysterious illness for lymphoma, but his inflamed lymph nodes were merely a red herring. A month after his initial hospitalization, pathologists at Mayo Clinic finally diagnosed him with idiopathic multicentric Castleman disease—a particularly ruthless form of a class of lymph node disorders that doesn't just attack one part of the body, but many, and has no known cause. It's a rare diagnosis within an already rare set of disorders. Only about 1,500 Americans a year receive the same diagnosis. </p><p>Without many options for treatment, Fajgenbaum underwent recurring rounds of chemotherapy. Each time, the treatment would offer temporary respite from Castleman symptoms, but bring the full spate of chemotherapy side effects. And it wasn't a sustainable treatment for the long haul. Regularly dousing a person's cells in unmitigated toxicity was about as elegant a solution to Fajgenbaum's disease as bulldozing a house in response to a toaster fire. The fire might go out (though not necessarily), but the house would be destroyed.</p><p>A swirl of exasperation and doggedness finally propelled Fajgenbaum to take on a crucial question himself: Among all of the already FDA-approved drugs on the market, was there something out there, labeled for another use, that could beat back Castleman disease and that he could tolerate long-term? After months of research, he discovered the answer: sirolimus, a drug normally prescribed to patients receiving a kidney transplant, could be used to suppress his overactive immune system with few known side effects to boot.</p><p>Fajgenbaum became hellbent on devoting his practice and research to making similar breakthroughs for others. He founded the Castleman Disease Collaborative Network, to coordinate the research of others studying this bewildering disease, and directs a laboratory consumed with studying cytokine storms—out-of-control immune responses characterized by the body's release of cytokines, proteins that the immune system secretes and uses to communicate with and direct other cells. </p><p>In the spring of 2020, when cytokine storms emerged as a hallmark of the most severe and deadly cases of COVID-19, Fajgenbaum's ears perked up. Although SARS-CoV-2 itself was novel, Fajgenbaum already had almost a decade of experience battling the most severe biological forces it brought. Only this time, he thought, it might actually be easier to pinpoint a treatment—unlike Castleman disease, which has no known cause, at least here a virus was clearly the instigator. </p>
Thinking Beyond COVID<p>The week of March 13, when the World Health Organization declared COVID-19 a pandemic, Fajgenbaum found himself hoping that someone would make the same connection and apply the research to COVID. "Then like a minute later I was like, 'Why am I hoping that someone, somewhere, either follows our footsteps, or has a similar background to us? Maybe we just need to do it," he says. And the CORONA Project was born—first as a 10-day exercise, and later as the robust, interactive tool it now is. </p><p>All of the 400 treatments in the CORONA database are examples of repurposed drugs, or off-label uses: physicians are prescribing drugs to treat COVID that have been approved for a different disease. There are no bonafide COVID treatments, only inferences. The goal for people like Fajgenbaum and Stone is to identify potential treatments for further study and eventual official approval, so that physicians can treat the disease with a playbook in hand. When it works, drug repurposing opens up a way to move quickly: A range of treatments could be available to patients within just a few years of a totally new virus entering our reality compared with the 12 - 19 years new drug development takes.</p><p>"Companies for many decades have explored the use of their products for not just a single indication but often for many indications," says Stone. "'Supplemental approvals' are all essentially examples of drug repurposing, we just didn't call it that. The challenge, I think, is to explore those opportunities more comprehensively and systematically to really try to understand the full breadth of potential activity of any drug or molecule."</p>
The left column shows the path of a repurposed drug, and on the right is the path of a newly discovered and developed drug.
Cures Within Reach
A Confounding Virus<p>The FDA declined to comment on what drugs it was fast-tracking for trials, but Fajgenbaum says that based on the CORONA Project's data, which includes data from smaller trials that have already taken place, he feels there are three drugs that seem the most clearly and broadly promising for large-scale studies. Among them are <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30503-8/fulltext" target="_blank" rel="noopener noreferrer"><u>dexamethasone</u></a>, which is a steroid with anti-inflammatory effects, and <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-combination-treatment-covid-19" target="_blank" rel="noopener noreferrer"><u>baricitinib</u></a>, a rheumatoid arthritis drug, both of which have enabled the sickest COVID-19 patients to bounce back by suppressing their immune systems. The third most clearly promising drug is <a href="https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients" target="_blank" rel="noopener noreferrer"><u>heparin</u></a>, a blood thinner, which a recent trial showed to be most helpful when administered at a full dose, more so than at a small, preventative dose. (On the flipside, Fajgenbaum says "it's a little sad" that in the database you can see hydroxychloroquine is still the most-prescribed drug being tried as a COVID treatment around the world, despite over the summer being <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2021801" target="_blank" rel="noopener noreferrer"><u>debunked</u></a> widely as an effective treatment, and continuously since then.)</p><p>One of the confounding attributes of SARS-CoV-2 is its ability to cause such a huge spectrum of outcomes. It's unlikely a silver bullet treatment will emerge under that reality, so the database also helps surface drugs that seem most promising for a specific population. <a href="https://jamanetwork.com/journals/jama/fullarticle/2773108" target="_blank" rel="noopener noreferrer"><u>Fluvoxamine</u></a>, a selective serotonin reuptake inhibitor used to treat obsessive compulsive disorder, showed promise in the recovery of outpatients—those who were sick, but not severely enough to be hospitalized. <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772185" target="_blank" rel="noopener noreferrer"><u>Tocilizumab</u></a>, which was actually developed for Castleman disease, the disease Fajgenbaum is managing, was initially written off as a COVID treatment because it failed to benefit large portions of hospitalized patients, but now seems to be effective if used on intensive care unit patients within 24 hours of admission—these are some of the sickest patients with the highest risk of dying. </p><p>Other than fluvoxamine, most of the drugs labeled as promising do skew toward targeting hospitalized patients, more than outpatients. One reason, Fajgenbaum says, is that "if you're in a hospital it's very easy to give you a drug and to track you, and there are very objective measurements as to whether you die, you progress to a ventilator, etc." Tracking outpatients is far more difficult, especially when folks have been routinely asked to stay home, quarantine, and free up hospital resources if they're experiencing only mild symptoms. </p><p>But the other reason for the skew is because COVID is very unlike most other diseases in terms of the human immune response the virus triggers. For example, if oncology treatments show some benefit to people with the highest risk of dying, then they usually work extremely well if administered in the earlier stages of a cancer diagnosis. Across many diseases, this dialing backward is a standard approach to identifying promising treatments. With COVID, all of that reasoning has proven moot. </p><p>As we've seen over the last year, COVID cases often start as asymptomatic, and remain that way for days, indicating the body is mounting an incredibly weak immune response initially. Then, between days five and 14, as if trying to make up for lost time, the immune system overcompensates by launching a major inflammatory response, which in the sickest patient can lead to the type of cytokine storms that helped Fajgenbaum realize his years of Castleman research might be useful during this public health crisis. Because of this phased response, you can't apply the same treatment logic to all cases.</p><p>"In COVID, drugs that work late tend to not work if given early, and drugs that work early tend to not work if given late," says Fajgenbaum. "Generally this … is not a commonplace thing for a virus." </p>
Thursday, March 11th, 2021 at 12:30pm - 1:45pm EST
On the one-year anniversary of the global declaration of the pandemic, this virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines. Planned topics include the effect of the new circulating variants on the vaccines, what we know so far about transmission dynamics post-vaccination, how individuals can behave post-vaccination, the myths of "good" and "bad" vaccines as more alternatives come on board, and more. A public Q&A will follow the expert discussion.
SPEAKERS:<img lazy-loadable="true" data-runner-src="https://leaps.org/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY3Mzc4NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjYwNjU4NX0.Tdrh5pze5P4XxgiJK3J4JFrsrijfabIzNJz-AATghDE/image.jpg?width=534&coordinates=365%2C3%2C299%2C559&height=462" id="87554" class="rm-shortcode" data-rm-shortcode-id="b6c7311be7aec25807f9af19b683bf1d" data-rm-shortcode-name="rebelmouse-image" data-width="534" data-height="462" />
Dr. Paul Offit speaking at Communicating Vaccine Science.commons.wikimedia.org<p><strong><a href="https://www.research.chop.edu/people/paul-a-offit" target="_blank" rel="noopener noreferrer">Dr. Paul Offit, M.D.</a>, is the director of the Vaccine Education Center and an attending physician in infectious diseases at the Children's Hospital of Philadelphia. He is a co-inventor of the rotavirus vaccine for infants, and he has lent his expertise to the advisory committees that review data on new vaccines for the CDC and FDA.</strong></p>
Dr. Monica Gandhi
UCSF Health<p><a href="https://profiles.ucsf.edu/monica.gandhi"></a><strong><a href="https://profiles.ucsf.edu/monica.gandhi" target="_blank">Dr. Monica Gandhi, M.D., MPH,</a> is Professor of Medicine and Associate Division Chief (Clinical Operations/ Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/ San Francisco General Hospital.</strong></p>
Dr. Onyema Ogbuagu, MBBCh, FACP, FIDSA
Yale Medicine<p><strong><a href="https://medicine.yale.edu/profile/onyema_ogbuagu/" target="_blank" rel="noopener noreferrer">Dr. Onyema Ogbuagu, MBBCh</a>, is an infectious disease physician at Yale Medicine who treats COVID-19 patients and leads Yale's clinical studies around COVID-19. He ran Yale's trial of the Pfizer/BioNTech vaccine.</strong></p>
Dr. Eric Topol
Dr. Topol's Twitter<p><strong><a href="https://www.scripps.edu/faculty/topol/" target="_blank" rel="noopener noreferrer">Dr. Eric Topol, M.D.</a>, is a cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute. He has led clinical trials in over 40 countries with over 200,000 patients and pioneered the development of many routinely used medications.</strong></p>