image:By creating a genome-proteome map scientists have uncovered hundreds of novel connections between different human diseases. view more

Credit: Omicscience https://www.omicscience.org/. This figure has been generated with BioRender.com.

Hundreds of connections between different human diseases have been uncovered through their shared origin in our genome by an international research team led by scientists from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, challenging the categorisation of diseases by organ, symptoms, or clinical speciality.

A new study published in Science today generated data on thousands of proteins circulating in our blood and combined this with genetic data to produce a map showing how genetic differences that affect these proteins link together seemingly diverse as well as related diseases.

Proteins are essential functional units of the human body that are composed of amino acids and coded for by our genes. Malfunctions of proteins cause diseases across most medical specialties and organ systems, and proteins are also the most common target of drugs that exist today.

The findings published today help explain why seemingly unrelated symptoms can occur at the same time in patients and suggest that we should reconsider how diverse diseases can be caused by the same underlying protein or mechanism. Where a protein is a drug target, this information can point to new strategies for treating a variety of conditions, as well as minimising adverse effects.

In the study using blood samples from over 10,000 participants from the Fenland study, the team led by senior author Dr Claudia Langenberg at the MRCEpidemiology Unit and Berlin Institute of Health at Charit Universittsmedizin, Germany, demonstrated that natural variation in 2,500 regions of the human genome is very robustly associated with differences in abundance or function of 5,000 proteins circulating in the blood.

This approach addresses an important bottleneck in the translation of basic science to clinically actionable insights. While large scale studies of the human genome have identified many thousands of variants in our DNA sequence that are associated with disease, underlying mechanisms remain often poorly understood due to uncertainties in mapping those variants to genes. By linking such disease-related DNA variations to the abundance or function of an encoded protein, the team produced strong evidence for which genes are involved, and identified novel mechanisms by which proteins mediate genetic risk into disease onset.

For example, multiple genome-wide association studies (GWAS) have linked a region of the human genome known as KAT8 with Alzheimers disease but failed to identify which gene in this region was involved. By combining data on both proteins and genes the team was able to identify a gene in the KAT8 region named PRSS8, which codes for the protein prostasin, as a novel candidate gene in Alzheimers disease. Similarly, they identified a novel risk gene for endometrial cancer (RSPO3).

The authors used these new insights to systematically test which of these protein-encoding genes affected a large range of diseases. They discovered more than 1,800 examples in which more than one disease was driven by variations in an individual gene and its protein products. What emerged was a network-like structure of human diseases, because many of the genes connected a range of seemingly diverse as well as related conditions in different tissues. This provides strong evidence that the respective protein is the origin, and points to new potential strategies for treatment.

Dr Langenberg explained:

An extreme example we discovered of how one protein can be connected to several diseases is the protein Fibulin-3, which we connected to 37 conditions, including hypermobility, hernias, varicose veins, and a lower risk of carpal tunnel syndrome. A likely explanation is atypical formation of elastic fibres covering our organs and joints, leading to differences in elasticity of soft and connective tissues. This is also in line with features that others have observed in mice where this gene was deleted.

Dr Maik Pietzner, a researcher at the MRC Epidemiology Unit and co-lead author of the study, added:

Using our genome as the basis was key to the success of this study. Because we know that most of the proteins detected in blood have their origin in cells from other tissues, we integrated different biological layers, like gene expression, to enable us to traceproteins back to disease-relevant tissues. For example, we found that higher activity of the enzyme bile salt sulfotransferase was associated with an increased risk of gall stones through a liver specific mechanism. We linked around 900 proteins to their tissue of origin in this way.

In collaboration with colleagues at the Helmholtz Centre in Munich, Germany, the authors have developed a bespoke web application (www.omicscience.org) to enable immediate dissemination of the results, and allow researchers worldwide to dive deeply into information on genes, proteins and diseases they are most interested in.

Dr Eleanor Wheeler, also at the MRC Epidemiology Unit and co-lead author of the study, concluded:

For most genomic regions associated with disease risk, the underlying causal gene and mechanism are not known. Our work demonstrates the distinctive value of proteins to zoom in on the causal gene for a disease and helps us to understand the mechanism through which genetic variation can cause disease. We envisage that the large amount of information we are sharing with the scientific community will help ongoing and emerging efforts to connect genes to diseases more directly via the encoded protein, thus facilitating accelerated identification of drug targets.

Reference

Pietzner M., Wheeler E., et al. Mapping the proteo-genomic convergence of human diseases. Science 2021;14 Oct 2021; DOI:10.1126/science.abj1541

ENDS

About the MRC Epidemiology Unit

The MRC Epidemiology Unit is a department at the University of Cambridge. It is working to improve the health of people in the UK and around the world.

Obesity, type 2 diabetes and related metabolic disorders present a major and growing global public health challenge. These disorders result from a complex interplay between genetic, developmental, behavioural and environmental factors that operate throughout life. The mission of the Unit is to investigate the individual and combined effects of these factors and to develop and evaluate strategies to prevent these diseases and their consequences. http://www.mrc-epid.cam.ac.uk

About the University of Cambridge

The University of Cambridge is one of the worlds top ten leading universities, with a rich history of radical thinking dating back to 1209. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence.

The University comprises 31 autonomous Colleges and 150 departments, faculties and institutions. Its 24,450 student body includes more than 9,000 international students from 147 countries. In 2020, 70.6% of its new undergraduate students were from state schools and 21.6% from economically disadvantaged areas.

Cambridge research spans almost every discipline, from science, technology, engineering and medicine through to the arts, humanities and social sciences, with multi-disciplinary teams working to address major global challenges. Its researchers provide academic leadership, develop strategic partnerships and collaborate with colleagues worldwide.

The University sits at the heart of the Cambridge cluster, in which more than 5,300 knowledge-intensive firms employ more than 67,000 people and generate 18 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK.

http://www.cam.ac.uk

About the Medical Research Council

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation. https://mrc.ukri.org/

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Mapping the proteo-genomic convergence of human diseases

14-Oct-2021

Robert A. Scott and Adrian Cortes are current employees and/or stockholders of GlaxoSmithKline. ERG receives an honorarium from the journal Circulation Research of the American Heart Association as a member of the Editorial Board. Stephen O'Rahilly has received remuneration for consultancy services provided to Pfizer Inc, Astra Zeneca, ERX Pharmaceuticals, GSK, Third Rock Ventures and LG Life Sciences. All other authors declare that they have no competing interests.

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Filling the gaps: connecting genes to diseases through proteins - EurekAlert

PALO ALTO, Calif., Oct. 12, 2021 /PRNewswire/ --BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical companythat focuses on genetic diseases and cancers, is announcing meaningful progress in its KRAS cancer portfolio, new programs in gene therapy, and advancements in cardiorenal and early-stage Mendelian programs at its second annual R&D Day today. BridgeBio will also discuss how it is broadening the scope of its R&D engine with the launch of its new early-stage research institute, BridgeBioX.

BridgeBio's R&D Day will feature presentations by Neil Kumar, Ph.D., BridgeBio founder and CEO; Richard Scheller, Ph.D., chairman of R&D at BridgeBio; Charles Homcy, M.D., chairman of pharmaceuticals at BridgeBio; Uma Sinha, Ph.D., chief scientific officer at BridgeBio; and scientists and physicians leading BridgeBio's drug discovery and development programs.

BridgeBio has more than 30 programs in its pipeline for patients living with genetic diseases and genetically-driven cancers. Fourteen of those programs are being advanced in the clinic or commercial setting, and earlier this year BridgeBio received its first two U.S. Food and Drug Administration (FDA) drug approvals.

R&D Day pipeline news and updates:

BridgeBio Precision Oncology

BridgeBio Gene Therapy

BridgeBio Cardiorenal

BridgeBioX

BridgeBio Mendelian

BridgeBio's R&D Day will be held today from 8:30 am ET 11:00 am ET and it will be webcast, with a link available in the event calendar on BridgeBio's investor website, https://investor.bridgebio.com/. A replay of the webcast will be available for one year following the event.

To register for BridgeBio's R&D Day, please sign uphere.

Agenda:

About BridgeBio Pharma, Inc.BridgeBio Pharma, Inc. (BridgeBio) is a biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio's pipeline of over 30 development programs ranges from early science to advanced clinical trials and its commercial organization is focused on delivering the company's two approved therapies. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.

BridgeBio Pharma, Inc. Forward-Looking StatementsThis press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include statements relating to expectations, plans and prospects regarding the preclinical and clinical development plans, clinical trial designs, clinical and therapeutic potential, and strategy of our product candidates, including, but not limited to: the unknown future impact of the COVID-19 pandemic delay on our ongoing development and/or our operations or operating expenses; the potential for our next-generation G12C dual inhibitors to be the first known compounds designed to directly bind and inhibit KRAS in both its active (GTP bound) and inactive (GDP bound) conformations driven by insights from its molecular dynamics platform; the potential of our precision oncology program and the timing of our selection of a RAS development candidate; the potential of BBP-818 to enable production of the GALT enzyme and to enable the body's natural ability to metabolize galactose in clinical trials; the potential and success of our Gene Therapy platform; the timing and success of BBP-711 for the treatment of primary hyperoxaluria type 1 and hyperoxaluria caused by hepatic overproduction of oxalate in recurrent kidney stone formers; the timing and success of acoramidis; the timing and success of our regulatory strategy for acoramidis; the timing and success of our planned meetings with regulatory health authorities, including the U.S. Food and Drug Administration (FDA), to discuss potential paths to registration prior to initiation of a Phase 3 registrational study of encaleret in patients with ADH1; the ability of encaleret to be the first approved therapy option indicated specifically for the treatment of ADH1; the success of BridgeBioX to test earlier scientific hypotheses in discovery research and target large, complex genetic diseases with high unmet need; the continuing success of our partnership with Stanford University; the timing and success of our Phase 2 trial of BBP-418; the potential for BBP-589 to be the only potential systemic treatment option being developed for patients with RDEB;reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to: initial and ongoing data from our preclinical studies and clinical trials not being indicative of final data; the potential size of the target patient populations our product candidates are designed to treat not being as large as anticipated; the design and success of ongoing and planned clinical trials, future regulatory filings, approvals and/or sales; despite having ongoing and future interactions with the FDA or other regulatory agencies to discuss potential paths to registration for our product candidates, the FDA or such other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; the continuing success of our collaborations; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; and those risks set forth in the Risk Factors section of our most recent annual report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and our other SEC filings. Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio's management as of the date of this release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

BridgeBio Media Contact:Grace Rauh[emailprotected](917) 232-5478

BridgeBio Investor Contact:Katherine Yau[emailprotected](516) 554-5989

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BridgeBio Pharma Announces Progress in its KRAS Portfolio, New Gene Therapy Programs, and Updates on Advancements Across its R&D Pipeline Targeting...

Damian Adams grew up knowing that his parents had used an anonymous sperm donor to conceive him, and as a teen, he was even proud of this identity. He considered donating to help other families have children. Becoming a father himself, however, changed everything. When his daughter was born 18 years ago, he cradled her in his arms, and he instantly saw himself in her and her in himself. He felt a biological connection so powerful that it made him reconsider his entire life up until then. What Id had there with my daughter, he says, was one thing I had been missing in my life. He felt the need to know where he came from.

Adams, a biologist in Australia, would spend years searching for his biological father, running into one dead end after another. Meanwhile, he also began campaigning to end donor anonymity for others like him. In 2016, he and fellow activists pushed the state of Victoria to retroactively abolish anonymity for all sperm donors. (A previous law had already banned it from 1998 onward.) Donor-conceived people in the United Kingdom have also successfully campaigned to ban anonymous sperm donation. In the United States, where anonymous donation is still technically offered, some donor-conceived people are asserting a right to know their genetic origins and even to contact their biological parents, who may or may not welcome the surprise.

All of this was unimaginable a few decades ago. Doctors used to routinely advise parents to keep the use of a sperm donor secreteven from their own childrenand this silence reinforced a sense of shame about the practice. Today, parents are strongly encouraged to tell the truth; moreover, DNA tests mean they couldnt hide it even if they wanted to. As more people find out they are donor-conceived, they are in turn finding one another: They are gathering in online communities such as We Are Donor Conceived and other Facebook support groups catering to a mix of donors, parents, donor-conceived people, and others who have learned that their parents are not who they thought they were. There are also several podcasts, at least two magazines, and even training courses for therapists who work with people in this situation. The shared identity that connects this online community is small by proportion but large in raw numbers. An estimated 30,000 to 60,000 children conceived with donor sperm are born in the U.S. every year, though that statistic may well be an underestimate. The fertility industry doesnt have to keep records, so the true number is unknown.

In learning more about their own conception, some donor-conceived people have been shocked by the lack of transparency in the industry that created them. They have been disturbed to find, in some cases, that they have dozens of half siblings from the same donor, that doctors have secretly impregnated patients with their own sperm, or that donors have lied about themselves to sperm banksall at least partially because donation was anonymous. Now donor-conceived people like Adams are questioning the need for any secrecy at all. In a forthcoming book called Uprooted, Peter Boni, who learned he was donor-conceived at age 49, lays out a Donor-Conceived Bill of Rights that demands, first and foremost, the end of anonymous donations and includes access to a donors medical records, limits on the number of offspring per donor, and consequences for outright fertility fraud. Can you point to any federal law, Boni asked me rhetorically, that protects the rights of the donor-conceived child?

Indeed, the agreements around sperm donations were originally forged among donors, parents, and doctors. Fast-forward a few decades and the childrennow adultsare trying to change a fertility industry that sees them as neither its customers nor its patients, even though it is directly responsible for their existence. The issues raised might apply to both sperm and egg donation alike, though historically, the focus has been on sperm donation because its much more common. As donor-conceived people advocate for new rights today, they are also forcing society to confront a more fundamental question, one left perhaps inadequately answered all those years ago: How much do biological ties really matter?

In a recent newsletter, the journalist Alison Motluk, who covers assisted reproduction, highlighted a discussion comparing three scenarios in which people were cut off from a biological parent:

One had a biological parent die before they were born. A second had a biological parent abscond before they were born. A third was conceived using an anonymous donor. Why do we acknowledge loss and feel empathy in the first two scenarios but not in the third?

I liked the way the question was framed, in terms of empathy rather than the harder-edged language of rights. Because when donor-conceived people ask for regulations on the exchange of sperm, they are also asking for acknowledgment that this biological exchange matters, that biological origins matter. We naturally recognize this in situations where a child has never met a parent owing to tragic life circumstancesso how does the situation then differ when the bond is severed by biotechnology instead? In my conversations with donor-conceived people, they often grappled with comparisons to more familiar scenarios. They are asking for rights, but they are also asking for compassion.

Tiffany Gardner, now 39 and an attorney in Atlanta, told me she had lost her father, Ken, to colon cancer when she was 4. Although Gardner later became close to her stepfather, she continued to treasure the few things she knew about Kenhe had been good at baseball and horseback riding, and she gravitated toward the same sports to maintain some kind of connection. At age 35, Gardner learned that her parents had actually used a sperm donor, and when she eventually found him, via a DNA test, parts of her identity suddenly clicked into place. She saw a photo of the donors son and it was, she told me, my face popping up as a dude. Her biological father had been an art teacher, and Gardner immediately linked that detail to her own longing to go to art school when she was younger. These connections made it all the more painful when the donors family objected to his having a relationship with her, and he abruptly cut her off.

To Gardner, her desire to connect with her biological fatherher actual biological father, this timewas not so different from her desire to stay connected with Ken. Her immediate family has been supportive, she said, but shes faced some pushback from acquaintances and older family members. Ive had a couple people that are sort of like, I dont get it. Those people arent really your family. Why do you want anything to do with this? she told me. But to Gardner, genetic ties clearly matteredif not, why did she spend her first 35 years trying to connect with a dead father she never really knew?

Adams began asking these same questions when he became a father. Not long after his daughters birth, it occurred to him that if he died right there and then, people would acknowledge the tragedy of his daughter never getting to know him. They would all recognize I was her father, he told me. Or, he went on, lets say, for example, a one-night stand. People recognize that as a tragedy, when that person is not in that childs life. Or in adoption, we recognize that as being problematic. The adoption world has in fact moved toward more and more open adoptions.

Isnt the difference, I asked, that sperm donation never promises, even implicitly, a relationship, and in fact in most cases explicitly disavows one before conception? To Adams, that disavowal made the situation even worsethat society would intentionally create people cut off from their biological parents. The genetic connection was, to him, immutable. If the connection really meant nothing, Adams said, why do many couples who use an egg or sperm donor still choose to have the child be related to one parent? It cant be that the connection is meaningful in one case but not in the other.

Not every donor-sperm-conceived personthey are, after all, a large groupfeels the same about the strength of genetic connection. In a 2020 survey conducted by We Are Donor Conceived in its own Facebook group and another called the Worldwide Donor Conceived People Network, 67 percent of respondents wanted the donors identity to be known from birth. Only 33 percent, though, felt that donors needed to be available for a relationship with the child from birth.

But its also impossible to survey the donor-conceived people who never join these groups, for whom this fact about their birth might feel unremarkable. Anecdotally, at least, this is common. Many of the donor-conceived people Ive talked with mentioned half siblings who never responded to messages through 23andMe or AncestryDNA, or who responded politely once and stopped there. Some people might feel very little curiosity about their biological origins, says Brianne Kirkpatrick, a genetic counselor who has helped many people through DNA discoveries. Some might feel that any curiosity would be betraying their family, and some are simply more interested in donor siblings than the donor. Age or stage of life may play into how people react differently, Kirkpatrick suggests, but theres not much research on why. What donor-conceived people want is a question few people asked until recently.

Sperm donation has already changed dramatically in the past three to four decades, and some of the changes that donor-conceived people are pushing have indeed happened, even if they are not necessarily enshrined in law. The secrecy around the use of donor sperm, for example, has dissipated as more single women and lesbian couples have openly used sperm banks. The ethics committee of the American Society of Reproductive Medicine (ASRM) now strongly encourages parents to tell their children if they were donor-conceived. Fertility doctors have also gone from procuring live sperm samples themselvescommonly from medical studentsto ordering frozen sperm from banks that can more thoroughly, if not always perfectly, screen donors. ASRM guidelines suggest that banks voluntarily limit the number of births per donor to 25 in a given population of 800,000 people. And sperm banks are more likely to offer open-ID donations, in which the donor can be contacted by his biological children. Some banks still have anonymous donations, in which they dont share any donor information. But these days, I think someone would have to be intentionally ignorant to not realize anonymity is not possible, Kirkpatrick says. Even without more formal regulation of sperm donation, widespread DNA testing means theres no more hiding in the passage of time.

These shifts have left plenty of gaps, though: Sperm banks, for example, do not have to keep track of births or coordinate with one another, so one donor could still be a prolific biological father. (There are donors with more than 100 biological children.) And in practice, anonymous donation still leaves the job of identifying a biological parent to the donor-conceived person. This could be easy enough if they are lucky and get a close DNA match such as a half sibling or first cousin, but it may be impossible or near-impossible if not. Some donor-conceived people have spent years searching.

Even so, the changing landscape of sperm donation is impossible to ignore, and donor-conceived children have grown up into adults who have their own opinions. At the ASRMs annual meeting in Baltimore next week, a panel is scheduled to discuss Open Identity Gamete Donation: What Are the Children Saying? (Gamete is the scientific term for egg or sperm.) But Erin Jackson, the founder of We Are Donor Conceived, pointed out to me that, despite the panels name, it features four experts and the mother of a donor-conceived sonbut not any children who are donor-conceived. To her, this just revealed how the fertility industry continues to ignore the people it helped create.

When I inquired with the ASRM, the organizations chief advocacy and policy officer, Sean Tipton, underplayed the importance of a single panel. So does ASRM have any plans to engage with the donor-conceived community? I asked. We very well might, Tipton said, without specifying what that would entail. He also questioned whether they were in fact the right people to engage: Were including patients a lot more in our organizations deliberations but, again, these are not patients. Furthermore, he added, a 30-year-old, donor-conceived person in 2021is that the right person to consult about somebody whos going through the process now? After all, none of us has a say in the circumstances of our conception, natural or otherwise. If donor-conceived people have the right to know about their genetic parentage, we should also consider how that right extends to other aspects of parent-child relationships and in other situations, says Judith Daar, the dean of Northern Kentucky Universitys law school and the former chair of the ASRM ethics committee that drafted guidelines for disclosure about donor conception in 2018. For example, she says, theres a debate in the infertility community whether a child had a right to know they were conceived through IVF, which may reveal aspects of the parents private reproductive history. And what about naturally conceived children, Daar askswhat do parents owe them about their sex lives?

Most people dont want to know how they were conceived, you know? Jackson said. Its not something you want to picture. For her, its medical, though. And, more important when donors and sperm banks are involved, its commercial. Money changes hands. Contracts are signed. The feeling of commodification is very real, she told me. The fertility industry is responsible for the creation of human beings; it is also a multibillion-dollar industry that is growing every year. Donors, doctors, and parents today, Jackson said, should be thinking more clearly about the futurebeyond holding a baby in their arms to what that baby will want when they grow up. She sees inspiration in the campaigns to abolish donor anonymity in the U.K. and parts of Australia, and she hopes to turn We Are Donor Conceived into a nonprofit, so that it might more forcefully advocate for changes.

Adams, in Australia, did eventually find his biological father, after multiple DNA tests and investigative work spanning years. (Though he got a donor number from medical records, the number didnt match anyone.) They look like spitting images of each other. Anybody whos seen the photos of the two of us can spot it instantaneously, he said. Theyve met in person and speak frequently on the phone. He finally found the connection he had been searching for, and now he wants others to find it too.

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Do We Have a Right to Know Our Biological Parents? - The Atlantic