Ironically, the technique, which is not entirely new, was developed in the United States and then forced offshore due to regulation. The precursor to MRT, known as cytoplasmic transfer, was pioneered in the late 1990s by Dr. Jacques Cohen and his team at the Saint Barnabas Institute in New Jersey. Cytoplasm is a jellylike substance that surrounds the nucleus and contains mitochondria. Treating a patient who had been trying to have a baby for ten years, Dr. Cohen suspected that there was a chance that some structure in the cytoplasm didn’t function optimally, and one of the major candidates was mitochondria. Dr. Cohen transferred a small amount of cytoplasm from a donor to his patient’s egg and then fertilized the egg with her husband’s sperm. Nine months later, long-awaited Alana was born. Sixteen more babies followed under Dr. Cohen’s care. Others copied the technique, and Dr. Cohen estimates that some thirty to fifty babies were born as a result of cytoplasmic transfer. But in 2002, the FDA stepped in and asked clinics to stop doing the procedure, citing safety and ethical concerns, particularly the theoretical concern about genetic modification. Since then, the procedure has not been performed in the United Sates.
Despite subsequent efforts to reverse this stance by the National Academies of Science, Engineering and Medicine as well as the FDA as the science has evolved, Congress remains firm in upholding its ban of the procedure. Paradoxically, some critics as well as proponents would like to see the procedure brought onshore. Noting what he calls “problems with the study,” in reference to Dr. Zhang’s work on mitochondrial replacement therapy, Dr. Dieter Egli of Columbia University Medical Center believes that the FDA should be overseeing these procedures. “For a technique pioneered and developed in the US, it [would] be fitting to see the benefits to patients here as well,” he wrote to NPR news. “Because of funding restrictions to the FDA, promising medical advances are forced to move elsewhere.”17
The British Parliament in 2015 voted to allow mitochondrial donation, making the United Kingdom the first country in the world to permit IVF babies to be created using biological material from three different people in order to help prevent serious genetic diseases. The British law allows for a procedure known as pronuclear transfer, which involves fertilizing both the mother’s egg and a donor egg with the father’s sperm. Before the fertilized eggs start dividing into early-stage embryos, their nuclei are removed. The nucleus from the donor’s fertilized egg is discarded and replaced by that from the mother’s fertilized egg. While critics, like in the United States, opposed the technique on ethical grounds, supporters, highlighting the pain and difficulty of caring for a child with a devastating disease, promoted the lifesaving benefits of MRT and countered critics by pointing out that having a third person’s DNA in your system is nothing new. Comparing the donation of mitochondria to his giving bone marrow to someone suffering from leukemia, Dr. Peter Braude, emeritus professor of obstetrics and gynecology at King’s College London, pointed out that from the transplant onward, the recipient will have DNA from Dr. Braude: “You won’t be related to me, you may be grateful to me, but you will have DNA from a third person circulating in your body.”18
The first baby conceived as a result of pronuclear transfer was born to a previously infertile mother on January 5, 2017, in Kiev, Ukraine.19 The mother, who did not suffer from mitochondrial disease, had tried unsuccessfully to have a baby for over a decade, with four failed IVF cycles.
* * *
Gene editing, while an entirely different technology from MRT, presents similar questions and challenges, particularly with respect to the ethics of altering the genetic line. In April 2015, a group of Chinese researchers sparked an international frenzy when they revealed that they had completed the world’s first experiments in editing genes in a human embryo—a technique that could potentially help prevent or eliminate genetic diseases and birth defects. Using the cutting-edge technology of a new gene editor called CRISPR-Cas9, which allows researchers to easily make precise cuts in the DNA of an embryo, the Chinese team tried to correct a mutation that causes a blood disease.20
The Chinese were quickly joined by Britain and Sweden. The United Kingdom’s Human Fertilisation and Embryology Authority (HFEA) in early 2016 approved research on editing the genomes of human embryos. Developmental biologist Dr. Kathy Niakan and her team at the Francis Crick Institute in London are editing genes in embryos that are active just after fertilization, and could potentially lead to treatments for infertility. After just seven days, the embryos will be destroyed. Dr. Fredrik Lanner of the Karolinska Institutet in Stockholm is similarly editing genes in viable human embryos with an eye to exploring early human development. Scientists speculate that there are more private groups out there doing this kind of work, but that they haven’t opened up their labs to public scrutiny.21
In August 2017, gene editing was conducted for the first time in the United States. A team of researchers, led by Dr. Shoukhrat Mitalipov, a reproductive biology specialist at the Oregon Health & Science University, successfully used CRISPR-Cas9 technology to correct the MYBPC3 gene that causes hypertrophic cardiomyopathy, a potentially fatal heart condition. Although the research is in early stages and must overcome regulatory and scientific hurdles prior to clinical use, researchers believe that in the future, this technique could be used in conjunction with PGD to help fix mutations in embryos that would otherwise be discarded. One of the biggest obstacles? The lack of federal funding for embryonic research.
The US bans on federal funding are likely to drive evolving technologies such as mitochondrial replacement therapy and gene editing, like most infertility research, to the private sector or overseas.22 Dr. Mitalipov, for example, said that he would be willing to move his research to the United Kingdom, if necessary.23
In 1974, Congress enacted a temporary moratorium on all federally funded clinical research on embryos and embryonic tissue, including research on IVF, infertility, and prenatal diagnosis, until national guidelines were established. Presumably sometime in the not-too-distant future. Forty-four years later, that moratorium is still in place, hampering not only progress in combatting infertility, but also the potential development of lifesaving therapies for a wide range of diseases. In addition to denying researchers much-needed funding and slowing scientific progress, the moratorium also deprives privately funded research (and therefore the public) of government oversight, which would, for example, verify that studies are carried out in an ethically acceptable way, protecting infertile couples that may be vulnerable to exploitation or ensuring that embryos are not used without consent or sold for profit.
With the rapid evolution of technology, how will doctors and lawmakers in the United States, which lacks comprehensive regulation of even basic IVF and other fertility treatments more than thirty-five years after their inception, be prepared to face questions raised by scientific advances? The future is upon us, and our policy makers cannot ignore it any longer.
Completing a book, it’s a little like having a baby.
John le Carré
Epilogue
Watching our children grow and develop into the independent little people that they are—catching glimpses of Alexandra dancing, and William building, and the two of them engaging in their own in-depth conversations—I sometimes find myself lost in thought, marveling at the very fact that they exist. I always knew how much I wanted them, but I never anticipated how much joy they would bring into our lives. Yet for every surge of joy, I know that there is another woman or man or couple out there who has not enjoyed such success, who has given up or is still trying—and I know we could be doing so much more to help them get there.
When I reflect on my long journey, on the many years of desperately wanting and trying, and finally ultimately succeeding against the odds to have our children, I’m aware of my own personal process of evolution—of how I changed irreversibly. Somewhere along the way, I transformed from a woman who was afraid of needles and resisted shots with all my might to a fearless warrior who mixed potions, loaded syringes,
and casually injected myself while talking to clients on speakerphone, in the ladies’ room in restaurants and nightclubs, and even once in the Moroccan desert on Christmas Eve. I morphed from a patient who didn’t believe I needed IVF to a client perpetually cycling through it, all in the effort to produce our two scientific miracles.
By the time our kids are old enough to read and understand the story of their conception, I am guessing that it will not be as unusual to contemplate that there were at least three—but closer actually to a dozen—people involved in bringing them into the world, rather than just the prince and princess they are accustomed to seeing in modern media. That there was Mom and Dad; and Catherine, our practically perfect surrogate; as well as the fertility specialists, embryologists, anesthesiologists, ultrasound technicians, acupuncturists, nurses, aides, midwives, and an alchemist. Not to mention those who helped us along the way down the paths not ultimately taken: the adoption specialists, home study social worker, other adoptive parents, and potential egg donors from around the world.
I imagine that their world will look quite different.
The future that I envision for our children is one in which these crucial gaps are closed. A world in which infertility treatment is viewed as a medical problem and covered by mainstream insurance policies. Where treatment is within reach financially for all who need and desire it. Where donors and surrogates are compensated fairly yet not astronomically.
A world in which patients are informed consumers of their treatment, aware of options and differing approaches. Where drugs are dispensed in a more incremental approach, rather than the kitchen-sink approach often used in America today. Where hormones are prescribed in the lowest effective dosages, both saving money and protecting the health of consumers.
A world in which federal funding is available to support research that advances scientific knowledge and informs both medical treatment and the establishment of sensible regulations.
I look at Alexandra and William and hope that they will live in such a world. It doesn’t seem too much to wish for, given that they already live in a world that was able to give them the miracle of life.
Afterword
BY DR. JOEL BATZOFIN,
MD, FACOG, Medical Director, New York Fertility Services, Manhattan, New York
Anyone who has struggled with infertility understands at a fundamental level just how all-consuming this problem can be. Not infrequently, a couple transitions from being concerned about the efficacy of a particular form of contraception to the realization that they have a problem conceiving. It takes courage to seek help for such an intimate aspect of one’s life. Sadly, in many cases, care can be the start of a long, challenging, and expensive journey through a maze of diagnostic tests and treatments. Some 15 to 20 percent of couples seeking to start or enlarge their family are affected by infertility.
As a consequence of her own years-long struggle with infertility, Elizabeth Katkin not only brings a wealth of knowledge and personal experience but also provides readers with useful insights she learned on her long, complex, transcontinental journey.
Katkin has lived, worked, and sought fertility treatments in different cities, countries, and continents. From her native United States to London, Dubai, and Russia, Katkin’s journey transformed her “from an ardent believer in following doctors’ orders to an active advocate” for herself. Readers of this book have learned about the complexities and challenges associated with a diagnosis of infertility. They have also learned about the importance of staying committed to the cause and about never giving up hope for solutions. Her story is a testament that no couples or individuals should remain involuntarily childless.
Katkin suffered infertility and multiple miscarriages as a consequence of polycystic ovarian syndrome, aneuploidy, as well as immune-related infertility. Any one of these complex problems can be challenging enough; together they at times may seem insurmountable. Fortunately, through the marvels of modern medicine, as well as her own commitment and the expertise of her doctors, Katkin and her husband are now the parents of two healthy children. Having been involved in this quest as a provider of care for some of the journey, I can attest to the persistence and unwavering devotion to the project that Elizabeth and her husband, Richard, demonstrated.
Through her personal story, hopefully Katkin has inspired readers to recognize that there is not a “one size fits all” approach to treatment. She challenges several conventional dogmas. Her story forces even the most experienced practitioner to question some of his or her own beliefs and practices. Furthermore, through the complex ethical, philosophical, and moral realities, readers pause and evaluate where they stand on some of the most pressing issues involved in reproductive medicine.
Recognizing that the practice of reproductive medicine is both a business as well as a treatment involving sophisticated high-tech solutions to complex medical problems, Katkin helps the reader to understand aspects of their care, which may not initially be readily apparent. She understands how vulnerable patients are, and she cautions them against falling into traps they may later regret. She encourages patients to recognize themselves as consumers and to undertake the necessary due diligence. Her legal expertise raises intelligent and provocative questions regarding regulatory aspects of the field. She addresses challenging concepts such as mitochondrial replacement therapy (so-called three-parent babies) and gene editing; disposal of unused embryos; custodial aspects of frozen embryos; and the sale of frozen embryos.
Conceivability is an extremely informative and well-researched book. Besides giving hope to anyone confronting this challenging disease called infertility, it is also a story of optimism and triumph. Katkin describes how she hopes her children will live in a world where patients avail themselves of state-of-the-art treatments, delivered safely, ethically, legally, and successfully anywhere they live in the world.
Any health-care provider involved in reproductive medicine, and any patient confronting this disease, will be happy they invested the time to read Conceivability. Readers are rewarded with finding answers to some vexing questions, as explained by a true fertility warrior, who has demonstrated amazing tenacity and persistence in search of her dreams.
Acknowledgments
Although it is long established that brevity is the soul of wit, I am afraid that in this case, I am simply unable to oblige, for there are far too many good souls to whom I am indebted.
This book started out as a thought on the beaches of Dubai in the months before William arrived, and evolved through conversations over coffee, hummus, and wine, through fits and starts, as the days turned into years. It was nurtured at the beginning and again at the end, both personally and professionally, by my good friend (very conveniently a book editor) Liza Darnton, who insisted from the beginning that I needed to write a Big Book, not just a memoir. Conceivability may never have emerged beyond my dreams, however, if I hadn’t been introduced to my very talented agent, Gillian MacKenzie, who saw the potential in this project and helped me to develop and refine my vision for the book. Thank you, Gillian.
I am so very grateful for Marysue Rucci, who took a bet on me, sharing my enthusiasm for bringing this information into the world, and helping me to shape an enormous, disparate mass of material into a relatable, digestible whole. Her intelligent questions and thoughtful reads pushed me to dig deeper. Many thanks as well to the marvelous team at Simon & Schuster, who all played key roles in launching Conceivability: Zachary Knoll, Christine Masters, Erica Ferguson, Amanda Lang, Lauren Carsley, and Dana Trocker.
Of course, there would be no book if there were no babies, and for that, I must thank my impressive, and extensive, medical team. First and foremost, Dr. Joel Batzofin, a wonderful doctor and now friend, treated us with so much care and respect, explaining every treatment each step of the way, and was never rushed for time. Without him, and Teresa and Kayee and the rest of his team, we would not have Alexandra. On the other side of the world, Dr. Oxana Bykovskaya and her team at Al
traVita opened my eyes to the possibility of a second child, and delivered on that promise, bringing William into our lives. Mr. Jeffrey Braithwaite, assisted by his wife and practice manager, Jane, and nurse Maria, treated us with tender, loving, and thoughtful care every step of the way, through uncountable exams and ultrasounds in support of our attempts, numerous miscarriages, and ultimately, two births.
And we had so much additional help from caring medical professionals along the way: Dr. Preston Sacks in DC; Drs. Yau Thum and Marie Wren at the Lister in London; Dr. Rachel Ashby at Brigham and Women’s in Massachusetts; Dr. Nataliya Petrova at the Cooper Health Clinic in Dubai; Dr. George Lewin at Southampton Medical Centre; the dedicated and caring nurses and midwives at the Maternity Unit at Ormskirk and District General Hospital who cared for all of us at the births of both Alexandra and William; and Dr. Victoria Muir of Belgrave Medical Centre and the kind staff of her baby clinic, who were always there for our family, before, during, and after the arrival of our beloved children. Special thanks as well to my outstanding acupuncturists and practitioners of traditional Chinese medicine: Dr. Mengda Shu in DC, who made me believe; Dr. Xiao-Ping Zhai of the Zhai Clinic in London; and the ever-ebullient Louisa Gordon, who saw me through, well, a lot. We are also eternally grateful to the amazing Ann Haigh, who skillfully and cheerfully steered us not only through the British parental order system but also through the unexpected complexity of obtaining William’s US passport.
I am also convinced that there would be neither book nor babies without the massive, unending support of my incredible family and friends who sustained me through years of infertility and miscarriage. While our network of friends spans several countries, I was fortunate to have a core group of amazing women in London who, with love, brainpower, care, and humor, saw me through my darkest days: Julie Lasso, Susan Namkung, Irene Chang, Kathryn Peterson, Sharon Benning, Trisha Johnson, Trish Thomas, Aleksandra Dochnal. How can I ever thank you? My dear friend Kathy Economy, from the beaches of Koh Samui to the hospital halls of the Brigham, has always had my back, and for this I am very grateful. Rod Baker, my friend and colleague, kindly led us through the English legal system, while other members of my Hogan “family”—Steve Robinson, Jeff Hurlburt, John Basnage, Mike Cheroutes, George Hagerty, Sean Harrison, Sharon Gray Edwards, Danielle Wood—somehow kept me together at work. Rustam Aksenenko and Svetlana Cheshinskaya supported our attempts and explorations from IVF to immunology to Russian adoption, from London to Geneva to Frankfurt to Moscow; no favor was too big or small. Jeffrey Costello and Olga Skorik counseled, housed, fed, translated for, transported, and ultimately celebrated with us; it’s a joy to see our Sashas and their younger brothers play together.
Conceivability_What I Learned Exploring the Frontiers of Fertility Page 26
