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.
The Death Predictor: A Helpful New Tool or an Ethical Morass?
Whenever Eric Karl Oermann has to tell a patient about a terrible prognosis, their first question is always: "how long do I have?" Oermann would like to offer a precise answer, to provide some certainty and help guide treatment. But although he's one of the country's foremost experts in medical artificial intelligence, Oermann is still dependent on a computer algorithm that's often wrong.
Doctors are notoriously terrible at guessing how long their patients will live.
Artificial intelligence, now often called deep learning or neural networks, has radically transformed language and image processing. It's allowed computers to play chess better than the world's grand masters and outwit the best Jeopardy players. But it still can't precisely tell a doctor how long a patient has left – or how to help that person live longer.
Someday, researchers predict, computers will be able to watch a video of a patient to determine their health status. Doctors will no longer have to spend hours inputting data into medical records. And computers will do a better job than specialists at identifying tiny tumors, impending crises, and, yes, figuring out how long the patient has to live. Oermann, a neurosurgeon at Mount Sinai, says all that technology will allow doctors to spend more time doing what they do best: talking with their patients. "I want to see more deep learning and computers in a clinical setting," he says, "so there can be more human interaction." But those days are still at least three to five years off, Oermann and other researchers say.
Doctors are notoriously terrible at guessing how long their patients will live, says Nigam Shah, an associate professor at Stanford University and assistant director of the school's Center for Biomedical Informatics Research. Doctors don't want to believe that their patient – whom they've come to like – will die. "Doctors over-estimate survival many-fold," Shah says. "How do you go into work, in say, oncology, and not be delusionally optimistic? You have to be."
But patients near the end of life will get better treatment – and even live longer – if they are overseen by hospice or palliative care, research shows. So, instead of relying on human bias to select those whose lives are nearing their end, Shah and his colleagues showed that they could use a deep learning algorithm based on medical records to flag incoming patients with a life expectancy of three months to a year. They use that data to indicate who might need palliative care. Then, the palliative care team can reach out to treating physicians proactively, instead of relying on their referrals or taking the time to read extensive medical charts.
But, although the system works well, Shah isn't yet sure if such indicators actually get the appropriate patients into palliative care. He's recently partnered with a palliative care doctor to run a gold-standard clinical trial to test whether patients who are flagged by this algorithm are indeed a better match for palliative care.
"What is effective from a health system perspective might not be effective from a treating physician's perspective and might not be effective from the patient's perspective," Shah notes. "I don't have a good way to guess everybody's reaction without actually studying it." Whether palliative care is appropriate, for instance, depends on more than just the patient's health status. "If the patient's not ready, the family's not ready and the doctor's not ready, then you're just banging your head against the wall," Shah says. "Given limited capacity, it's a waste of resources" to put that person in palliative care.
The algorithm isn't perfect, but "on balance, it leads to better decisions more often."
Alexander Smith and Sei Lee, both palliative care doctors, work together at the University of California, San Francisco, to develop predictions for patients who come to the hospital with a complicated prognosis or a history of decline. Their algorithm, they say, helps decide if this patient's problems – which might include diabetes, heart disease, a slow-growing cancer, and memory issues – make them eligible for hospice. The algorithm isn't perfect, they both agree, but "on balance, it leads to better decisions more often," Smith says.
Bethany Percha, an assistant professor at Mount Sinai, says that an algorithm may tell doctors that their patient is trending downward, but it doesn't do anything to change that trajectory. "Even if you can predict something, what can you do about it?" Algorithms may be able to offer treatment suggestions – but not what specific actions will alter a patient's future, says Percha, also the chief technology officer of Precise Health Enterprise, a product development group within Mount Sinai. And the algorithms remain challenging to develop. Electronic medical records may be great at her hospital, but if the patient dies at a different one, her system won't know. If she wants to be certain a patient has died, she has to merge social security records of death with her system's medical records – a time-consuming and cumbersome process.
An algorithm that learns from biased data will be biased, Shah says. Patients who are poor or African American historically have had worse health outcomes. If researchers train an algorithm on data that includes those biases, they get baked into the algorithms, which can then lead to a self-fulfilling prophesy. Smith and Lee say they've taken race out of their algorithms to avoid this bias.
Age is even trickier. There's no question that someone's risk of illness and death goes up with age. But an 85-year-old who breaks a hip running a marathon should probably be treated very differently than an 85-year-old who breaks a hip trying to get out of a chair in a dementia care unit. That's why the doctor can never be taken out of the equation, Shah says. Human judgment will always be required in medical care and an algorithm should never be followed blindly, he says.
Experts say that the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully.
Researchers are also concerned that their algorithms will be used to ration care, or that insurance companies will use their data to justify a rate increase. If an algorithm predicts a patient is going to end up back in the hospital soon, "who's benefitting from knowing a patient is going to be readmitted? Probably the insurance company," Percha says.
Still, Percha and others say, the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully. "These are new and exciting tools that have a lot of potential uses. We need to be conscious about how to use them going forward, but it doesn't mean we shouldn't go down this road," she says. "I think the potential benefits outweigh the risks, especially because we've barely scratched the surface of what big data can do right now."
“Young Blood” Transfusions Are Not Ready For Primetime – Yet
The world of dementia research erupted into cheers when news of the first real victory in a clinical trial against Alzheimer's Disease in over a decade was revealed last October.
By connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier.
Alzheimer's treatments have been famously difficult to develop; 99 percent of the 200-plus such clinical trials since 2000 have utterly failed. Even the few slight successes have failed to produce what is called 'disease modifying' agents that really help people with the disease. This makes the success, by the midsize Spanish pharma company Grifols, worthy of special attention.
However, the specifics of the Grifols treatment, a process called plasmapheresis, are atypical for another reason - they did not give patients a small molecule or an elaborate gene therapy, but rather simply the most common component of normal human blood plasma, a protein called albumin. A large portion of the patients' normal plasma was removed, and then a sterile solution of albumin was infused back into them to keep their overall blood volume relatively constant.
So why does replacing Alzheimer's patients' plasma with albumin seem to help their brains? One theory is that the action is direct. Alzheimer's patients have low levels of serum albumin, which is needed to clear out the plaques of amyloid that slowly build up in the brain. Supplementing those patients with extra albumin boosts their ability to clear the plaques and improves brain health. However, there is also evidence suggesting that the problem may be something present in the plasma of the sick person and pulling their plasma out and replacing it with a filler, like an albumin solution, may be what creates the purported benefit.
This scientific question is the tip of an iceberg that goes far beyond Alzheimer's Disease and albumin, to a debate that has been waged on the pages of scientific journals about the secrets of using young, healthy blood to extend youth and health.
This debate started long before the Grifols data was released, in 2014 when a group of researchers at Stanford found that by connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier. There was something either present in young blood that allowed tissues to regenerate, or something present in old blood that prevented regeneration. Whatever the biological reason, the effects in the experiment were extraordinary, providing a startling boost in health in the older mouse.
After the initial findings, multiple research groups got to work trying to identify the "active factor" of regeneration (or the inhibitor of that regeneration). They soon uncovered a variety of compounds such as insulin-like growth factor 1 (IGF1), CCL11, and GDF11, but none seemed to provide all the answers researchers were hoping for, with a number of high-profile retractions based on unsound experimental practices, or inconclusive data.
Years of research later, the simplest conclusion is that the story of plasma regeneration is not simple - there isn't a switch in our blood we can flip to turn back our biological clocks. That said, these hypotheses are far from dead, and many researchers continue to explore the possibility of using the rejuvenating ability of youthful plasma to treat a variety of diseases of aging.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence.
The data remain intriguing because of the astounding results from the conjoined circulatory system experiments. The current surge in interest in studying the biology of aging is likely to produce a new crop of interesting results in the next few years. Both CCL11 and GDF11 are being researched as potential drug targets by two startups, Alkahest and Elevian, respectively.
Without clarity on a single active factor driving rejuvenation, it's tempting to try a simpler approach: taking actual blood plasma provided by young people and infusing it into elderly subjects. This is what at least one startup company, Ambrosia, is now offering in five commercial clinics across the U.S. -- for $8,000 a liter.
By using whole plasma, the idea is to sidestep our ignorance, reaping the benefits of young plasma transfusion without knowing exactly what the active factors are that make the treatment work in mice. This space has attracted both established players in the plasmapheresis field – Alkahest and Grifols have teamed up to test fractions of whole plasma in Alzheimer's and Parkinson's – but also direct-to-consumer operations like Ambrosia that just want to offer patients access to treatments without regulatory oversight.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence. We simply haven't performed trials to test whether dosing a mostly healthy person with plasma can slow down aging, at least not yet. There is some evidence that plasma replacement works in mice, yes, but those experiments are all done in very different systems than what a human receiving young plasma might experience. To date, I have not seen any plasma transfusion clinic doing young blood plasmapheresis propose a clinical trial that is anything more than a shallow advertisement for their procedures.
The efforts I have seen to perform prophylactic plasmapheresis will fail to impact societal health. Without clearly defined endpoints and proper clinical trials, we won't know whether the procedure really lowers the risk of disease or helps with conditions of aging. So even if their hypothesis is correct, the lack of strong evidence to fall back on means that the procedure will never spread beyond the fringe groups willing to take the risk. If their hypothesis is wrong, then people are paying a huge amount of money for false hope, just as they do, sadly, at the phony stem cell clinics that started popping up all through the 2000s when stem cell hype was at its peak.
Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.
The real progress in the field will be made slowly, using carefully defined products either directly isolated from blood or targeting a bloodborne factor, just as the serious pharma and biotech players are doing already.
The field will progress in stages, first creating and carefully testing treatments for well-defined diseases, and only then will it progress to large-scale clinical trials in relatively healthy people to look for the prevention of disease. Most of us will choose to wait for this second stage of trials before undergoing any new treatments. Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.