Vanessa Colimorio (left) and Sharon Kochlany (right) at a farm with their four-year-old twin daughters and one-year-old son. The kids share the same sperm donor.
Sharon Kochlany and Vanessa Colimorio's four-year-old twin girls had a classic school assignment recently: make a family tree. They drew themselves and their one-year-old brother branching off from their moms, with aunts, uncles, and grandparents forking off to the sides.
The recently-gained sovereignty of queer families stands to be lost if a consumer DNA test brings a stranger's identity out of the woodwork.
What you don't see in the invisible space between Kochlany and Colimorio, however, is the sperm donor they used to conceive all three children.
To look at a family tree like this is to see in its purest form that kinship can supersede biology—the boundaries of where this family starts and stops are clear to everyone in it, in spite of a third party's genetic involvement. This kind of self-definition has always been synonymous with LGBTQ families, especially those that rely on donor gametes (sperm or eggs) to exist.
But the world around them has changed quite suddenly: The recent consumer DNA testing boom has made it more complicated than ever for families built through reproductive technology—openly, not secretively—to maintain the strong sense of autonomy and privacy that can be crucial for their emotional security. Prospective parents and cryobanks are now mulling how best to bring a new generation of donor-conceived people into this world in a way that leaves open the choice to know more about their ancestry without obliterating an equally important choice: the right not to know about biological relatives.
For queer parents who have long fought for social acceptance, having a biological relationship to their children has been revolutionary, and using an unknown donor as a means to this end especially so. Getting help from a friend often comes with the expectation that the friend will also have social involvement in the family, which some people are comfortable with, but being able to access sperm from an unknown donor—which queer parents have only been able to openly do since the early 1980s—grants them the reproductive autonomy to create families seemingly on their own. That recently-gained sovereignty stands to be lost if a consumer DNA test brings a stranger's identity out of the woodwork.
At the same time, it's natural for donor-conceived people to want to know more about where they come from ethnically, even if they don't want to know the identity of their donor. As a donor-conceived person myself, I know my donor's self-reported ethnicity, but have often wondered how accurate it is.
Opening the Pandora's box of a consumer DNA test as a way to find out has always felt profoundly unappealing to me, however. Many people have accidentally learned they're donor-conceived by unwittingly using these tools, but I already know that about myself going in, and subsequently know I'll be connected to a large web of people whose existence I'm not interested in learning about. In addition to possibly identifying my anonymous donor, his family could also show up, along with any donor-siblings—other people with whom I share a donor. My single lesbian mom is enough for me, and the trade off to learn more about my ethnic ancestry has never seemed worth it.
In 1992, when I was born, no one was planning for how consumer DNA tests might upend or illuminate one's sense of self. But the donor community has always had to stay nimble with balancing privacy concerns and psychological well-being, so it should come as no surprise that figuring out how to do so in 2020 includes finding a way to offer ancestry insight while circumventing consumer DNA tests.
A New Paradigm
This is the rationale behind unprecedented industry news that LeapsMag can exclusively break: Within the next few weeks, California Cryobank, the largest cryobank in the country, will begin offering genetically-verified ancestry information on the free public part of every donor's anonymous profile in its database, something no other cryobanks yet offer (an exact launch date was not available at the time of publication). Currently, California Cryobank's donor profiles include a short self-reported list that might merely say, "Ancestry: German, Lebanese, Scottish."
The new information will be a report in pie chart form that details exactly what percentages of a donor's DNA come from up to 26 ethnicities—it's analogous to, but on a smaller scale than, the format offered by consumer DNA testing companies, and uses the same base technology that looks for single nucleotide polymorphisms in DNA that are associated with specific ethnicities. But crucially, because the donor takes the DNA test through California Cryobank, not a consumer-facing service, the information is not connected in a network to anyone else's DNA test. It's also taken before any offspring exist so there's no chance of revealing a donor-conceived person's identity this way.
Later, when a donor-conceived person is born, grows up, and wants information about their ethnicity from the donor side, all they need is their donor's anonymous ID number to look it up. The donor-conceived person never takes a genetic test, and therefore also can't accidentally find donor siblings this way. People who want to be connected to donor siblings can use a sibling registry where other people who want to be found share donor ID numbers and look for matches (this is something that's been available for decades, and remains so).
"With genetic testing, you have no control over who reaches out to you, and at what point in your life."
California Cryobank will require all new donors to consent to this extra level of genetic testing, setting a new standard for what information prospective parents and donor-conceived people can expect to have. In the immediate, this information will be most useful for prospective parents looking for donors with specific backgrounds, possibly ones similar to their own.
It's a solution that was actually hiding in plain sight. Two years ago, California Cryobank's partner Sema4, the company handling the genetic carrier testing that's used to screen for heritable diseases, started analyzing ethnic data in its samples. That extra information was being collected because it can help calculate a more accurate assessment of genetic risks that run in certain populations—like Ashkenazi Jews and Tay Sachs disease—than relying on oral family histories. Shortly after a plan to start collecting these extra data, Jamie Shamonki, chief medical officer of California Cryobank, realized the companies would be sitting on a goldmine for a different reason.
"I didn't want to use one of these genetic testing companies like Ancestry to accomplish this," says Shamonki. "The whole thing we're trying to accomplish is also privacy."
Consumer-facing DNA testing companies are not HIPAA compliant (whereas Sema4, which isn't direct-to-consumer, is HIPAA compliant), which means there are no legal privacy protections covering people who add their DNA to these databases. Although some companies, like 23andMe, allow users to opt-out of being connected with genetic relatives, the language can be confusing to navigate, requires a high level of knowledge and self-advocacy on the user's part, and, as an opt-out system, is not set up to protect the user from unwanted information by default; many unwittingly walk right into such information as a result.
Additionally, because consumer-facing DNA testing companies operate outside the legal purview that applies to other health care entities, like hospitals, even a person who does opt-out of being linked to genetic relatives is not protected in perpetuity from being re-identified in the future by a change in company policy. The safest option for people with privacy concerns is to stay out of these databases altogether.
For California Cryobank, the new information about donor heritage won't retroactively be added to older profiles in the system, so donor-conceived people who already exist won't benefit from the ancestry tool, but it'll be the new standard going forward. The company has about 500 available donors right now, many of which have been in their registry for a while; about 100 of those donors, all new, will have this ancestry data on their profiles.
Shamonki says it has taken about two years to get to the point of publicly including ancestry information on a donor's profile because it takes about nine months of medical and psychological screening for a donor to go from walking through the door to being added to their registry. The company wanted to wait to launch until it could offer this information for a significant number of donors. As more new donors come online under the new protocol, the number with ancestry information on their profiles will go up.
For Parents: An Unexpected Complication
While this change will no doubt be welcome progress for LGBTQ families contemplating parenthood, it'll never be possible to put this entire new order back in the box. What are such families who already have donor-conceived children losing in today's world of widespread consumer genetic testing?
Kochlany and Colimorio's twins aren't themselves much older than the moment at-home DNA testing really started to take off. They were born in 2015, and two years later the industry saw its most significant spike. By now, more than 26 million people's DNA is in databases like 23andMe and Ancestry; as a result, it's estimated that within a year, 90 percent of Americans of European descent will be identifiable through these consumer databases, by way of genetic third cousins, even if they didn't want to be found and never took the test themselves. This was the principle behind solving the Golden State Killer cold case.
The waning of privacy through consumer DNA testing fundamentally clashes with the priorities of the cyrobank industry, which has long sought to protect the privacy of donor-conceived people, even as open identification became standard. Since the 1980s, donors have been able to allow their identity to be released to any offspring who is at least 18 and wants the information. Lesbian moms pushed for this option early on so their children—who would obviously know they couldn't possibly be the biological product of both parents—would never feel cut off from the chance to know more about themselves. But importantly, the openness is not a two-way street: the donors can't ever ask for the identities of their offspring. It's the latter that consumer DNA testing really puts at stake.
"23andMe basically created the possibility that there will be donors who will have contact with their donor-conceived children, and that's not something that I think the donor community is comfortable with," says I. Glenn Cohen, director of Harvard Law School's Center for Health Law Policy, Biotechnology & Bioethics. "That's about the donor's autonomy, not the rearing parents' autonomy, or the donor-conceived child's autonomy."
Kochlany and Colimorio have an open identification donor and fully support their children reaching out to California Cryobank to get more information about him if they want to when they're 18, but having a singular name revealed isn't the same thing as having contact, nor is it the same thing as revealing a web of dozens of extended genetic relations. Their concern now is that if their kids participate in genetic testing, a stranger—someone they're careful to refer to as only "the donor" and never "dad"—will reach out to the children to begin some kind of relationship. They know other people who are contemplating giving their children DNA tests, and feel staunchly that it wouldn't be right for their family.
"With genetic testing, you have no control over who reaches out to you, and at what point in your life," Kochlany says. "[People] reaching out and trying to say, 'Hey I know who your dad is' throws a curveball. It's like, 'Wait, I never thought I had a dad.' It might put insecurities in their minds."
"We want them to have the opportunity to choose whether or not they want to reach out," Colimorio adds.
Kochlany says that when their twins are old enough to start asking questions, she and Colimorio plan to frame it like this: "The donor was kind of like a technology that helped us make you a person, and make sure that you exist," she says, role playing a conversation with their kids. "But it's not necessarily that you're looking to this person [for] support or love, or because you're missing a piece."
It's a line in the sand that's present even for couples still far off from conceiving. When Mallory Schwartz, a film and TV producer in Los Angeles, and Lauren Pietra, a marriage and family therapy associate (and Shamonki's step-daughter), talk about getting married someday, it's a package deal with talking about how they'll approach having kids. They feel there are too many variables and choices to make around family planning as a same-sex couple these days to not have those conversations simultaneously. Consumer DNA databases are already on their minds.
"It frustrates me that the DNA databases are just totally unregulated," says Schwartz. "I hope they are by the time we do this. I think everyone deserves a right to privacy when making your family [using a sperm donor]."
"I wouldn't want to create a world where people who are donor-conceived feel like they can't participate in this technology because they're trying to shut out [other] information."
On the prospect of having a donor relation pop up non-consensually for a future child, Pietra says, "I don't like it. It would be really disappointing if the child didn't want [contact], and unfortunately they're on the receiving end."
You can see how important preserving the right to keep this door closed is when you look at what's going on at The Sperm Bank of California. This pioneering cryobank was the first in the world to openly serve LGBTQ people and single women, and also the first to offer the open identification option when it opened in 1982, but not as many people are asking for their donor's identity as expected.
"We're finding a third of young people are coming forward for their donor's identity," says Alice Ruby, executive director. "We thought it would be a higher number." Viewed the other way, two-thirds of the donor-conceived people who could ethically get their donor's identity through The Sperm Bank of California are not asking the cryobank for it.
Ruby says that part of what historically made an open identification program appealing, rather than invasive or nerve-wracking, is how rigidly it's always been formatted around mutual consent, and protects against surprises for all parties. Those [donor-conceived people] who wanted more information were never barred from it, while those who wanted to remain in the dark could. No one group's wish eclipsed the other's. The potential breakdown of a system built around consent, expectations, and respect for privacy is why unregulated consumer DNA testing is most concerning to her as a path for connecting with genetic relatives.
For the last few decades in cryobanks around the world, the largest cohort of people seeking out donor sperm has been lesbian couples, followed by single women. For infertile heterosexual couples, the smallest client demographic, Ruby says donor sperm offers a solution to a medical problem, but in contrast, it historically "provided the ability for [lesbian] couples and single moms to have some reproductive autonomy." Yes, it was still a solution to a biological problem, but it was also a solution to a social one.
The Sperm Bank of California updated its registration forms to include language urging parents, donor-conceived people, and donors not to use consumer DNA tests, and to go through the cryobank if they, understandably, want to learn more about who they're connected to. But truthfully, there's not much else cryobanks can do to protect clients on any side of the donor transaction from surprise contact right now—especially not from relatives of the donor who may not even know someone in their family has donated sperm.
A Tricky Position
Personally, I've known I was donor-conceived from day one. It has never been a source of confusion, angst, or curiosity, and in fact has never loomed particularly large for me in any way. I see it merely as a type of reproductive technology—on par with in vitro fertilization—that enabled me to exist, and, now that I do exist, is irrelevant. Being confronted with my donor's identity or any donor siblings would make this fact of my conception bigger than I need it to be, as an adult with a full-blown identity derived from all of my other life experiences. But I still wonder about the minutiae of my ethnicity in much the same way as anyone else who wonders, and feel there's no safe way for me to find out without relinquishing some of my existential independence.
"People obviously want to participate in 23andMe and Ancestry because they're interested in knowing more about themselves," says Shamonki. "I wouldn't want to create a world where people who are donor-conceived feel like they can't participate in this technology because they're trying to shut out [other] information."
After all, it was the allure of that exact conceit—knowing more about oneself—that seemed to magnetically draw in millions of people to these tools in the first place. It's an experience that clearly taps into a population-wide psychic need, even—perhaps especially—if one's origins are a mystery.
Sammy Basso is one of around 400 young people in the world with progeria.
Just 400 or so people in the world live with progeria: The mutation that causes it usually arises de novo, or "of new," meaning that it is not inherited but happens spontaneously during gestation. The challenge, as with all rare diseases, is that few cases means few treatments.
"When we first started, there was absolutely nothing out there," says Leslie Gordon, a physician-researcher who co-founded the Progeria Research Foundation in 1999 after her own son, also named Sam, was diagnosed with the disease. "We knew we had to jumpstart the entire field, so we collected money through road races and special events and writing grants and all sorts of donors… I think the first year we raised $75,000, most of it from one donor."
"We have not only the possibility but the responsibility to make the world a better world, and also to make a body a better body."
By 2003, the foundation had collaborated with Francis Collins, a geneticist who is now director of the National Institutes of Health, to work out the genetic basis for progeria—that single mutation Sammy has. The discovery led to interest in lonafarnib, a drug that was already being used in cancer patients but could potentially operate downstream of the mutation, preventing the buildup of the defective progerin in the body. "We funded cellular studies to look at a lonafarnib in cells, mouse studies to look at lonafarnib in mouse models of progeria… and then we initiated the clinical trials," Gordon says.
Sammy Basso's family had gotten involved with the Progeria Research Foundation through their international patient registry, which maintains relationships with families in 49 countries. "We started to hear about lonafarnib in 2006 from Leslie Gordon," says Sammy's father, Amerigo Basso, with his son translating. "She told us about the lonafarnib. And we were very happy because for the first time we understood that there was something that could help our son and our lives." Amerigo used the Italian word speranza, which means hope.
Still, Sammy wasn't sure if lonafarnib was right for him. "Since when I was very young I thought that everything happens for a reason. So, in my mind, if God made me with progeria, there was a reason, and to try to heal from progeria was something wrong," he says. Gradually, his parents and doctors, and Leslie Gordon, convinced him otherwise. Sammy began to believe that God was also the force behind doctors, science, and research. "And so we have not only the possibility but the responsibility to make the world a better world, and also to make a body a better body," he says.
Sammy Basso and his parents.
Courtesy of Basso
Sammy began taking lonafarnib, with the Progeria Research Foundation intermittently flying him, and other international trial participants, to Boston for tests. He was immediately beset by some of the drug's more unpleasant side effects: Stomach problems, nausea, and vomiting. "The first period was absolutely the worst period of my life," he says.
At first, doctors prescribed other medicines for the side effects, but to Sammy it had as much effect as drinking water. He visited doctor after doctor, with some calling him weekly or even daily to ask how he was doing. Eventually the specialists decided that he should lower his dose, balancing his pain with the benefit of the drug. Sammy can't actually feel any positive effect of the lonafarnib, but his health measurements have improved relative to people with progeria who don't take it.
While they never completely disappeared, Sammy's side effects decreased to the point that he could live. Inspired by the research that led to lonafarnib, he went to university to study molecular biology. For his thesis work, he travelled to Spain to perform experiments on cells and on mice with progeria, learning how to use the gene-editing technique CRISPR-Cas9 to cut out the mutated bit of DNA. "I was so excited to participate in this study," Sammy says. He felt like his work could make a difference.
In 2018, the Progeria Research Foundation was hosting one of their biennial workshops when Francis Collins, the researcher who had located the mutation behind progeria 15 years earlier, got in touch with Leslie Gordon. "Francis called me and said, Hey, I just saw a talk by David Liu from the Broad [Institute]. And it was pretty amazing. He has been looking at progeria and has very early, but very exciting data… Do you have any spaces, any slots you could make in your program for late breaking news?"
Gordon found a spot, and David Liu came to talk about what was going on in his lab, which was an even more advanced treatment that led to mice with the progeria mutation living into their senior mouse years—substantially closer to a normal lifespan. Liu's lab had built on the idea of CRISPR-Cas9 to create a more elegant genetic process called base editing: Instead of chopping out mutated DNA, a scientist could chemically convert an incorrect DNA letter to the correct one, like the search and replace function in word processing software. Mice who had their Lamin-A mutations corrected this way lived more than twice as long as untreated animals.
Sammy was in the audience at Dr. Liu's talk. "When I heard about this base editing as a younger scientist, I thought that I was living in the future," he says. "When my parents had my diagnosis of progeria, the science knew very little information about DNA. And now we are talking about healing the DNA… It is incredible."
Lonafarnib (also called Zokinvy) was approved by the US Food and Drug Administration this past November. Sammy, now 25, still takes it, and still manages his side effects. With luck, the gift of a few extra years will act as a bridge until he can try Liu's revolutionary new gene treatment, which has not yet begun testing in humans. While Leslie Gordon warns that she's always wrong about things like this, she hopes to see the new base editing techniques in clinical trials in the next year or two. Sammy won't need to be convinced to try it this time; his thinking on fate has evolved since his first encounter with lonafarnib.
"I would be very happy to try it," he says. "I know that for a non-scientist it can be difficult to understand. Some people think that we are the DNA. We are not. The DNA is a part of us, and to correct it is to do what we are already doing—just better." In short, a gene therapy, while it may seem like science fiction, is no different from a pill. For Sammy, both are a new way to think about fate: No longer something that simply happens to him.
There is a lot to be optimistic about regarding the new safe and highly effective vaccines, which are moving society closer toward the goal of close human contact once again.
To be clear, these vaccine candidates for COVID-19, both authorized and not yet authorized, are highly effective and safe. In fact, across all trials and sites, all six vaccines were 100% effective in preventing hospitalizations and death from COVID-19.
All Vaccines' Phase 3 Clinical Data
Complete protection against hospitalization and death from COVID-19 exhibited by all vaccines with phase 3 clinical trial data.
This astounding level of protection from SARS-CoV-2 from all vaccine candidates across multiple regions is likely due to robust T cell response from vaccination and will "defang" the virus from the concerns that led to COVID-19 restrictions initially: the ability of the virus to cause severe illness. This is a time of hope and optimism. After the devastating third surge of COVID-19 infections and deaths over the winter, we finally have an opportunity to stem the crisis – if only people readily accept the vaccines.
Amidst these incredible scientific advancements, however, public health officials and politicians have been pushing downright discouraging messaging. The ubiquitous talk of ongoing masks and distancing restrictions without any clear end in sight threatens to dampen uptake of the vaccines. It's imperative that we break down each concern and see if we can revitalize our public health messaging accordingly.
The first concern: we currently do not know if the vaccines block asymptomatic infection as well as symptomatic disease, since none of the phase 3 vaccine trials were set up to answer this question. However, there is biological plausibility that the antibodies and T-cell responses blocking symptomatic disease will also block asymptomatic infection in the nasal passages. IgG immunoglobulins (generated and measured by the vaccine trials) enter the nasal mucosa and systemic vaccinations generate IgA antibodies at mucosal surfaces. Monoclonal antibodies given to outpatients with COVID-19 hasten viral clearance from the airways.
Although it is prudent for those who are vaccinated to wear masks around the unvaccinated in case a slight risk of transmission remains, two fully vaccinated people can comfortably abandon masking around each other.
Moreover, data from the AztraZeneca trial (including in the phase 3 trial final results manuscript), where weekly self-swabbing was done by participants, and data from the Moderna trial, where a nasal swab was performed prior to the second dose, both showed risk reductions in asymptomatic infection with even a single dose. Finally, real-world data from a large Pfizer-based vaccine campaign in Israel shows a 50% reduction in infections (asymptomatic or symptomatic) after just the first dose.
Therefore, the likelihood of these vaccines blocking asymptomatic carriage, as well as symptomatic disease, is high. Although it is prudent for those who are vaccinated to wear masks around the unvaccinated in case a slight risk of transmission remains, two fully vaccinated people can comfortably abandon masking around each other. Moreover, as the percentage of vaccinated people increases, it will be increasingly untenable to impose restrictions on this group. Once herd immunity is reached, these restrictions can and should be abandoned altogether.
The second concern translating to "doom and gloom" messaging lately is around the identification of troubling new variants due to enhanced surveillance via viral sequencing. Four major variants circulating at this point (with others described in the past) are the B.1.1.7 variant ("UK variant"), B.1.351 ("South Africa variant), P.1. ("Brazil variant"), and the L452R variant identified in California. Although the UK variant is likely to be more transmissible, as is the South Africa variant, we have no reason to believe that masks, distancing and ventilation are ineffective against these variants.
Moreover, neutralizing antibody titers with the Pfizer and Moderna vaccines do not seem to be significantly reduced against the variants. Finally, although the Novavax 2-dose and Johnson and Johnson (J&J) 1-dose vaccines had lower rates of efficacy against moderate COVID-19 disease in South Africa, their efficacy against severe disease was impressively high. In fact J&J's vaccine still prevented 100% of hospitalizations and death from COVID-19. When combining both hospitalizations/deaths and severe symptoms managed at home, the J&J 1-dose vaccine was 85% protective across all three sites of the trial: the U.S., Latin America (including Brazil), and South Africa.
In South Africa, nearly all cases of COVID-19 (95%) were due to infection with the B.1.351 SARS-CoV-2 variant. Finally, since herd immunity does not rely on maximal immune responses among all individuals in a society, the Moderna/Pfizer/J&J vaccines are all likely to achieve that goal against variants. And thankfully, all of these vaccines can be easily modified to boost specifically against a new variant if needed (indeed, Moderna and Pfizer are already working on boosters against the prominent variants).
The third concern of some public health officials is that people will abandon all restrictions once vaccinated unless overly cautious messages are drilled into them. Indeed, the false idea that if you "give people an inch, they will take a mile" has been misinforming our messaging about mitigation since the beginning of the pandemic. For example, the very phrase "stay at home" with all of its non-applicability for essential workers and single individuals is stigmatizing and unrealistic for many. Instead, the message should have focused on how people can additively reduce their risks under different circumstances.
The public will be more inclined to trust health officials if those officials communicate with nuanced messages backed up by evidence, rather than with broad brushstrokes that shame. Therefore, we should be saying that "vaccinated people can be together with other vaccinated individuals without restrictions but must protect the unvaccinated with masks and distancing." And we can say "unvaccinated individuals should adhere to all current restrictions until vaccinated" without fear of misunderstandings. Indeed, this kind of layered advice has been communicated to people living with HIV and those without HIV for a long time (if you have HIV but partner does not, take these precautions; if both have HIV, you can do this, etc.).
Our heady progress in vaccine development, along with the incredible efficacy results of all of them, is unprecedented. However, we are at risk of undermining such progress if people balk at the vaccine because they don't believe it will make enough of a difference. One of the most critical messages we can deliver right now is that these vaccines will eventually free us from the restrictions of this pandemic. Let's use tiered messaging and clear communication to boost vaccine optimism and uptake, and get us to the goal of close human contact once again.