SCOOP: Largest Cryobank in the U.S. to Offer Ancestry Testing
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.
The author and her mom in spring of 1998.
"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.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Trying to get a handle on CRISPR news in 2019 can be daunting if you haven't been avidly reading up on it for the last five years.
CRISPR as a diagnostic tool would be a major game changer for medicine and agriculture.
On top of trying to grasp how the science works, and keeping track of its ever expanding applications, you may also have seen coverage of an ongoing legal battle about who owns the intellectual property behind the gene-editing technology CRISPR-Cas9. And then there's the infamous controversy surrounding a scientist who claimed to have used the tool to edit the genomes of two babies in China last year.
But gene editing is not the only application of CRISPR-based biotechnologies. In the future, it may also be used as a tool to diagnose infectious diseases, which could be a major game changer for medicine and agriculture.
How It Works
CRISPR is an acronym for a naturally occurring DNA sequence that normally protects microbes from viruses. It's been compared to a Swiss army knife that can recognize an invader's DNA and precisely destroy it. Repurposed for humans, CRISPR can be paired with a protein called Cas9 that can detect a person's own DNA sequence (usually a problematic one), cut it out, and replace it with a different sequence. Used this way, CRISPR-Cas9 has become a valuable gene-editing tool that is currently being tested to treat numerous genetic diseases, from cancer to blood disorders to blindness.
CRISPR can also be paired with other proteins, like Cas13, which target RNA, the single-stranded twin of DNA that viruses rely on to infect their hosts and cause disease. In a future clinical setting, CRISPR-Cas13 might be used to diagnose whether you have the flu by cutting a target RNA sequence from the virus. That spliced sequence could stick to a paper test strip, causing a band to show up, like on a pregnancy test strip. If the influenza virus and its RNA are not present, no band would show up.
To understand how close to reality this diagnostic scenario is right now, leapsmag chatted with CRISPR pioneer Dr. Feng Zhang, a molecular biologist at the Broad Institute of MIT and Harvard.
What do you think might be the first point of contact that a regular person or patient would have with a CRISPR diagnostic tool?
FZ: I think in the long run it will be great to see this for, say, at-home disease testing, for influenza and other sorts of important public health [concerns]. To be able to get a readout at home, people can potentially quarantine themselves rather than traveling to a hospital and then carrying the risk of spreading that disease to other people as they get to the clinic.
"You could conceivably get a readout during the same office visit, and then the doctor will be able to prescribe the right treatment right away."
Is this just something that people will use at home, or do you also foresee clinical labs at hospitals applying CRISPR-Cas13 to samples that come through?
FZ: I think we'll see applications in both settings, and I think there are advantages to both. One of the nice things about SHERLOCK [a playful acronym for CRISPR-Cas13's longer name, Specific High-sensitivity Enzymatic Reporter unLOCKing] is that it's rapid; you can get a readout fairly quickly. So, right now, what people do in hospitals is they will collect your sample and then they'll send it out to a clinical testing lab, so you wouldn't get a result back until many hours if not several days later. With SHERLOCK, you could conceivably get a readout during the same office visit, and then the doctor will be able to prescribe the right treatment right away.
I just want to clarify that when you say a doctor would take a sample, that's referring to urine, blood, or saliva, correct?
FZ: Right. Yeah, exactly.
Thinking more long term, are there any Holy Grail applications that you hope CRISPR reaches as a diagnostic tool?
FZ: I think in the developed world we'll hopefully see this being used for influenza testing, and many other viral and pathogen-based diseases—both at home and also in the hospital—but I think the even more exciting direction is that this could be used and deployed in parts of the developing world where there isn't a fancy laboratory with elaborate instrumentation. SHERLOCK is relatively inexpensive to develop, and you can turn it into a paper strip test.
Can you quantify what you mean by relatively inexpensive? What range of prices are we talking about here?
FZ: So without accounting for economies of scale, we estimate that it can cost less than a dollar per test. With economy of scale that cost can go even lower.
Is there value in developing what is actually quite an innovative tool in a way that visually doesn't seem innovative because it's reminiscent of a pregnancy test? And I don't mean that as an insult.
FZ: [Laughs] Ultimately, we want the technology to be as accessible as possible, and pregnancy test strips have such a convenient and easy-to-use form. I think modeling after something that people are already familiar with and just changing what's under the hood makes a lot of sense.
Feng Zhang
(Photo credit: Justin Knight, McGovern Institute)
It's probably one of the most accessible at-home diagnostic tools at this point that people are familiar with.
FZ: Yeah, so if people know how to use that, then using something that's very similar to it should make the option very easy.
You've been quite vocal in calling for some pauses in CRISPR-Cas9 research to make sure it doesn't outpace the ethics of establishing pregnancies with that version of the tool. Do you have any concerns about using CRISPR-Cas13 as a diagnostic tool?
I think overall, the reception for CRISPR-based diagnostics has been overwhelmingly positive. People are very excited about the prospect of using this—for human health and also in agriculture [for] detection of plant infections and plant pathogens, so that farmers will be able to react quickly to infection in the field. If we're looking at contamination of foods by certain bacteria, [food safety] would also be a really exciting application.
Do you feel like the controversies surrounding using CRISPR as a gene-editing tool have overshadowed its potential as a diagnostics tool?
FZ: I don't think so. I think the potential for using CRISPR-Cas9 or CRISPR-Cas12 for gene therapy, and treating disease, has captured people's imaginations, but at the same time, every time I talk with someone about the ability to use CRISPR-Cas13 as a diagnostic tool, people are equally excited. Especially when people see the very simple paper strip that we developed for detecting diseases.
Are CRISPR as a gene-editing tool and CRISPR as a diagnostics tool on different timelines, as far as when the general public might encounter them in their real lives?
FZ: I think they are all moving forward quite quickly. CRISPR as a gene-editing tool is already being deployed in human health and agriculture. We've already seen the approval for the development of growing genome-edited mushrooms, soybeans, and other crop species. So I think people will encounter those in their daily lives in that manner.
Then, of course, for disease treatment, that's progressing rapidly as well. For patients who are affected by sickle cell disease, and also by a degenerative eye disease, clinical trials are already starting in those two areas. Diagnostic tests are also developing quickly, and I think in the coming couple of years, we'll begin to see some of these reaching into the public realm.
"There are probably 7,000 genetic diseases identified today, and most of them don't have any way of being treated."
As far its limits, will it be hard to use CRISPR as a diagnostic tool in situations where we don't necessarily understand the biological underpinnings of a disease?
FZ: CRISPR-Cas13, as a diagnostic tool, at least in the current way that it's implemented, is a detection tool—it's not a discovery tool. So if we don't know what we're looking for, then it's going to be hard to develop Cas13 to detect it. But even in the case of a new infectious disease, if DNA sequencing or RNA sequencing information is available for that new virus, then we can very rapidly program a Cas13-based system to detect it, based on that sequence.
What's something you think the public misunderstands about CRISPR, either in general, or specifically as a diagnostic tool, that you wish were better understood?
FZ: That's a good question. CRISPR-Cas9 and CRISPR-Cas12 as gene editing tools, and also CRISPR-Cas13 as a diagnostic tool, are able to do some things, but there are still a lot of capabilities that need to be further developed. So I think the potential for the technology will unfold over the next decade or so, but it will take some time for the full impact of the technology to really get realized in real life.
What do you think that full impact is?
FZ: There are probably 7,000 genetic diseases identified today, and most of them don't have any way of being treated. It will take some time for CRISPR-Cas9 and Cas12 to be really developed for addressing a larger number of those diseases. And then for CRISPR-based diagnostics, I think you'll see the technology being applied in a couple of initial cases, and it will take some time to develop that more broadly for many other applications.