Fertilized Eggs Versus Embryos, An Ongoing Failure of Terminology

“What is an Embryo?” Connecticut Law Review, 2004, with forward by Ruth Bader Ginsberg.

Nature does not regard fertilized human eggs as children. Nature’s stringent biological requirements of a fertilized egg leads to miscarriage far more often than successful pregnancy. Fewer than 10% of eggs fertilized in fertility clinics have the biological potential to develop into a child. Nature has evolved rigorous developmental milestones to avoid wasting precious maternal uterus time on a fertilized egg without the capacity for successful development to birth. It’s a numbers’ game. The nine months of human pregnancy means nine eggs will not have the opportunity to be released by the ovary for fertilization, so the fertilized egg occupying the maternal resources needs to prove it is worth the loss of nine other chances to continue the species. 

Nature does not regard fertilized human eggs as children.

These facts are well known to reproductive biologists, but those scientists have failed to adequately communicate these basic reproductive principles to everyone, including the legal and ethical scholars striving to protect the interests of the least of us, the human embryo. When fertilization of a human egg could be observed routinely in laboratories decades ago, the scientists and clinicians involved had the responsibility to develop new terminology to accurately describe the early stages of human development never before seen. The privacy of the union of human egg and sperm had been breached, and that breach deserved new and more accurate  language for clarity (1).

The confusion caused by the lack of clear  terminology has exacerbated the age-old question of “When does life begin?” This is an important religious and ethical concern for societies striving to value all human life and promote the continued advancement of enlightened understanding of what it means to be human. But nature has relentlessly demonstrated it does not share this concern for individual fertilized eggs. Maternal resources are not to be squandered on the weak or defective, those fertilized eggs are unabashedly rejected rapidly by the maternal environment, whereas in laboratory dishes they may be allowed to limp along for a few days and perhaps even preserved in liquid nitrogen storage by well meaning scientists on the futile hope they are more robust than they appear. 

Dictionaries before ART defined “embryo” as beginning two to four weeks following fertilization and before the fetal developmental period.

Before assisted reproduction for humans was developed, animal eggs fertilized in laboratories were referred to simply as “fertilized eggs”, the term “embryo” was not applied because it was well known by the scientists conducting the experiments that early development was driven by the egg itself. A better term for “fertilized egg” was desperately needed, but not developed, so the erroneous term of “embryo” was applied by clinicians in early programs of assisted reproductive technology (ART). Dictionaries before ART defined “embryo” as beginning two to four weeks following fertilization, before the fetal developmental period (1). This unfortunate lack of attention to accurate terminology has lead to decades of rancorous debate about the ethical and legal status of eggs fertilized in ART laboratories. 

Day one, fertilized human egg.

Nature is not so confused. A fertilized egg has to prove it is biologically relevant before it is worthy of maternal attention. The most well known signal to the mother is the pregnancy test, a protein synthesized by the fertilized egg as it enters the embryo stage. That embryonic signal must increase daily for the first 10 to 12 weeks after fertilization, or the developing embryo, or fetus, is unceremoniously rejected by miscarriage. This natural loss allows a new egg the opportunity to be fertilized and prove its worthiness. The viability of the species depends on this rigorous attention to the fitness of its offspring.

It is not too late for scientists and clinicians to develop terminology that accurately describes nature’s view of “when does life begin?” The inadequate term “embryo” not only fails to be useful, it invokes unnecessary rancor among social bodies striving to support our very humanity. We need to get this right. 

(1) “What is an embryo?” Connecticut Law Review, 2004. Law Review Rejoinder.

Download this Science Highlights PDF – Feb 2024.

What is an Embryo?

[Check out this month’s Science Highlights “Fertilized Eggs Versus Embryos, An Ongoing Failure of Terminology.]

In light of the recent news from Alabama, we are reposting “What Is An Embryo?”.

This is the first comprehensive look at the influence of accurate science terminology, published by the Connecticut Law Review along with rejoinders by Dr. Harold Shapiro, Prof John A. Robertson, Prof Lars Noah, and Father Kevin P. Quinn.

The law review addresses the controversy of all of the entities that are currently called “embryos” with regards to embryonic stem cell research legislation around the world.

Download the PDF: What Is an Embryo? 

“Ann Kiessling’s thoughtful and extremely useful review covers a good deal of history, language, and public policy intimately related to the controversial technologies that surround the use of embryos either in biomedical research or ART.”
– Harold T. Shapiro, Emeritus, Princeton University

 

“No one would deny that the subtleties of human embryology are neglected in public debate. This alone should compel scientists to choose terms that make scientific sense and to provide clear definitions. Dr. Kiessling has accepted well that challenge. But I also think that Kiessling is up to something else in her essay. She is attempting to reposition science, to gain for it a more influential voice in the heated politics of embryonic discourse.”
– Kevin P. Quinn, S. J. Professor of Law, Georgetown University Law Center

Connecticut Law Review Stem CellsI. INTRODUCTION AND DEFINITION OF THE PROBLEM

“Most scientific and medical discoveries are accompanied by new terms to describe the new processes. Although this imposes the burden on society of continually learning a new lexicon, new terminology clarifies that the societal impact of emerging technologies needs to be newly interpreted.”
– Excerpt, page 1, Ann A. Kiessling, PhD

“As stated in the Commentary, the goal was not to try to re-define existing moral and ethical views of tasks undertaken by eggs, especially ‘when life begins’ but to try to make room in those views for the emerging biomedical technologies that are currently dependent upon the innate capabilities of human eggs.”
– Excerpt, page 2, “Rejoinder,” Ann A. Kiessling, PhD

DOWNLOADS

Connecticut Law Review: What Is an Embryo?

Read the rejoinder: What is an Embryo?: A Rejoinder

Download brochure (pdf)

2023 Activated Egg Symposium Talks are Live

​On October 27th, Bedford Research held the Activated Egg Symposium in Downtown Boston. This year’s topic was “Human Egg Activation: The Influence of Sperm” with Keynotes: David Keefe, MD, NYU, speaking on “Retrotransposition and early embryo development,” and Oliver Rando, PhD, UMass, speaking on “Epigenetic contributions of sperm to early development in mammals.”

Dr. Rando is an internationally recognized pioneer in the epigenetic influence of sperm on egg fertilization and resulting offspring development in murine models. And Dr. Keefe is an internationally recognized clinician scientist whose early work focused on the role of telomeres in mammalian gametes and has more recently been involved in studies of parthenogenesis and retroelement expression.

The day was a fantastic event bringing together investigators from academia, industry and infertility clinics. All of the talks are now posted live on the Symposium Website (link below)

Watch Past Talks

Bedford Research Foundation 2022 Newsletter

Read about all of the progress and the research that has occurred at the Foundation over the course of the past year, and a retrospective on the past 26!


Stem Cells For EveryBody

Twenty-Six Years of Progress

Founded in 1996 to conduct research that cannot be funded by the National Institutes of Health, Bedford Research scientists have achieved ground-breaking milestones!

See our Timeline of Milestones!

[Pictured Right: Green fluorescent protein glow in the nuclei of a two-cell mouse embryo provides new insights for deriving stem cells from artificially activated eggs.]

Read More

Bedford Research Foundation 2021 Newsletter

Read about all of the progress and the research that has occurred at the Foundation over the course of the past year, and a retrospective on the past 25!


Stem Cells For EveryBody

Twenty-Five Years of Progress

Founded in 1996 to conduct research that cannot be funded by the National Institutes of Health, Bedford Research scientists have achieved ground-breaking milestones!

See our Timeline of Milestones!

Read More

New Staff at BRF

The Foundation is ready for 2022 with these new staff additions.

Dr. David Albertini joins the foundation as Professor of Reproductive Cell Biology. He is a leading Embryologist, Editor-in-Chief of the Journal of Assisted Reproduction and Genetics, and visiting scientist at The Rockefeller University and Center for Human Reproduction. Dr. Albertini’s most recent research at the Bedford Research Foundation aims to develop clinically useful stem cells from activated human eggs and understand the mechanisms underlying ovarian and oocyte aging in women.

María Gracia Gervasi joins the Bedford Research Foundation as Assistant Professor of Reproductive Cell Biology. Her scientific career is dedicated to studying the molecular pathways regulating sperm acquisition of fertilization competence. She is pursuing research regarding the parthenogenetic activation of human oocytes to develop human stem cells.

In addition to her research, Maria is passionate about working towards a more inclusive and diverse environment in science. Since 2020, she has organized a series of bi-weekly international seminars online (Reproseminars) specifically designed to bring together the Hispanic/Latin community working in reproductive biology around the globe.

Dr. Lynae Brayboy joins us as Associate Professor of Reproductive Cell Biology. Dr. Brayboy is board certified in Reproductive Endocrinology with a passion for understanding egg biology: “Life begins with an egg, and we don’t know very much about them.” Dr. Brayboy is currently on sabbatical in Germany, pursuing her research into egg mitochondrial function. She graduated from Florida A&M University followed by medical degree from Temple University and residency in obstetrics and gynecology. Women and Infants Hospital was the location for her clinical fellowship in reproductive endocrinology. Dr. Brayboy’s passion for egg research is a welcome addition to our parthenote stem cell derivation program.
Katherine Bertolini, B.S. graduated from Boston University with a bachelor’s degree in biology. She started at Bedford Research in September 2021 as a PVSA intern. She is excited to expand her role at the Bedford Research Foundation as a lab technician. Originally from York, Maine, Katherine grew up sailing competitively and eventually went on to end her senior year at Boston University as a captain of the BU sailing team. When she is not at the lab, she spends much of her time outside enjoying nature

Who is Bedford Research Foundation?

David Albertini Biography

Yesterday we posted an announcement of David Albertini joining the Bedford Research Foundation as Professor and Chair of the Department of Developmental Cell Biology.

Biography/ Background

David Albertini received his Ph.D. in 1975 from Harvard University working on the cell biology of the mammalian ovary. After postdoctoral work at the University of Connecticut Health Center, he returned to Harvard Medical School as an Assistant Professor of Anatomy and Cell Biology from 1977-1984, and was Professor at Tufts University Schools of Medicine until 2004. At Tufts, he served as Chair of the Department of Anatomy and Cell Biology (1996-2000), Director of the Center for Reproduction (1999-2003) and Director of the Confocal Microscopy core (1988-1999). From 2004-2016, he was Hall Professor of Molecular Medicine at the Kansas University Medical Center. In 2016 he became the Director of Laboratories and Senior Scientist at the Center for Human Reproduction in New York City. He serves as the Editor-in-Chief of the Journal of Assisted Reproduction and Genetics, an official journal of the American Society for Reproductive Medicine (2009-present). In 2020, David joined the Bedford Research Foundation team where he continues his research interests in reproductive medicine and biology. He is the recipient of many awards including a Basil O’Connor fellowship from the March of Dimes, the Hammond Medal from the Society for Reproduction and Fertility (UK), and the Founder’s Lecturer for the Australian Society of Reproductive Biology, The Beacon Award FIR course MBL, and recently was recognized as an Honorary Member of the International Society for In Vitro Fertilization (ISIVF). He is presently a Visiting Scientist at The Rockefeller University and Center for Human Reproduction, continues to serve on scientific advisory boards, and is a frequent invited speaker here and abroad. His most recent research at the Bedford Research Foundation is aimed at developing clinically useful stem cells from activated human eggs and understanding the mechanisms underlying ovarian and oocyte aging in women.

Useful Links:

Journal of Assisted Reproduction and Genetics (JARG)

David Albertini on Google Scholar

Springer Nature – Trending Topics in IVF: Guest Blog by David F. Albertini

Ovarian Stem Cells: prematurely speaking (Video)

SIG Embryology: interview Prof. Dr. David Albertini (Video)

Dr. David Albertini, Leading Embryologist and Editor of the Journal of Assisted Reproduction and Genetics, Joins BRF

Amidst the chaos of COVID-19 this year, the BRF has welcomed a new member to their stem cell research team. Professor David Albertini formalized his commitment to advancing the cause of therapeutic stem cell program at the BRF by accepting the position of Professor and Chair of the Department of Developmental Cell Biology. David’s more than 40 year career in reproductive medicine has addressed the basic cellular mechanisms underlying how eggs are built within the ovary and how once activated, by sperm or artificial means, the process of embryonic development is launched. It is this latter dimension of his background that he is pursuing with Dr. Ann Kiessling and colleagues at BRF as they attempt to derive embryonic stem cells from human eggs that have been artificially activated.

Dr. Albertini

Dr. Albertini speaks at the 2019 Activated Egg Symposium in Boston.

David has been a leader in the use of egg cells to produce viable embryos initially using animal models and over the past 20 years, his efforts have focused on how to improve the quality of human eggs and embryos as measured by their ability to yield healthy offspring after transfer back into patients. From this work, David was a member of the team that developed human oocyte freezing back in the 2000s. David has also been a leader in the field of biomedical imaging of living embryos and stem cells and in 2019, moved one of his high-powered live cell imaging systems to the BRF where it has become an important tool for the research going on there.

“BRF is an incredibly unique organization that is doing potentially life-saving research that cannot be done in large federally funded labs, I am thrilled to be joining the team.” – Dr Albertini

A key project that David has taken on since joining the BRF is that of making parthenogenetic embryos from human eggs from which we plan to derive “patient-specific” stem cells. Patient-specific cells would help solve the ongoing problem of tissue rejection that exists with many current stem cell therapies. Using oocytes obtained from young “egg bank” donors, the team has been able to develop methodology assuring maturation of eggs that when presented with activating stimuli result in development of embryos containing only a female (maternal) genome. The BRF team had previously demonstrated the feasibility of making stem cells from such “parthenotes” in mice and even achieved genetic engineering of the resultant stem cells. To reach the same goal with human eggs, that in the end could provide a source of therapeutic stem cells for patients in need, is the overarching aim of the BRF program, enriched as it now is with the addition of David.

Microscope photo of a A three-cell parthenote

A three-cell human parthenote developed at BRF.

In addition to his research prowess, David has been a dedicated educator and academician holding appointments at Harvard, Tufts, Kansas University Medical Center, and The Rockefeller University. He has trained over 50 Ph.D. students, and post-doctoral fellows and has been widely recognized as a lecturer, meeting organizer, and recipient of honorary awards for research excellence from professional societies around the world. His formal involvement with the BRF also means that the BRF becomes the official editorial office for the Journal of Assisted Reproduction and Genetics, a journal of the American Society for Reproductive Medicine that he has been Editor-in-Chief of since the summer of 2009.

And finally, as noted above, David is a local product having been raised in nearby Hudson, MA and receiving his Ph.D. from the Division of Medical Sciences at the Harvard Medical School (in 1975). He is thrilled to be back in the neighborhood where his lifelong aspirations to contribute to humanity through the lens of contemporary biomedical science will continue to flourish.

We look forward to sending more updates on our research progress with Dr. Albertini in the New Year.

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