Grandiose visions of gene-editing tool CRISPR’s ability to change! revolutionize! transform! the world recently reached a zenith of absurdity in a WIRED cover story titled The Genesis Engine. The article triggered the Twitter hashtag #CRISPRfacts, which for days was devoted to poking fun at the overly optimistic tenor of CRISPR’s press. But the financial world is viewing CRISPR dreams as no laughing matter.
On August 10, Editas Medicine announced that Bill Gates, Google Ventures, Deerfield Management, and other investors have funded CRISPR to the tune of $120 million. In what seems to be a case of self-fulfilling prophecy, the biotech financial press declared that money changes everything, or as one headline put it, “CRISPR: Editas’ $120M proves it isn’t a bunch of hype.”
The $120 million investment takes place amid a CRISPR patent fight between two Editas co-founders: Feng Zhang (Broad Institute) and CRISPR’s celebrated innovator Jennifer Doudna (UC Berkeley) who has since left Editas. It’s the largest round of financing yet for CRISPR, though as Xconomy noted, it’s only a fraction of the private biotech financing record set by Moderna Therapeutics earlier in 2015, when it raised $450 million for messenger RNA drug development.
So there’s a lot going on behind the scenes. Bill Gates and Google, of course, have their hands deep in other pies of sexy research funding including Gates’ backing of Wi-Fi activated birth control (speculated to arrive in 2018) or Calico’s “longevity research.”
One of the striking points of the recent funding announcement is the first condition Editas is targeting, a rare form of genetic blindness called leber congenital amaurosis (LCA) that affects roughly 1,000 people in the United States – well under the 200,000-person number that qualifies as an “orphan disease.” Those 1,000 people may be seeking medical help, and it’s certainly possible that a CRISPR treatment for LCA will turn out to be a step toward treating other diseases. But it’s an important point to consider.
A recent article by Ronald Bayer and Sandro Galea in the New England Journal of Medicine, "Public Health in the Era of Precision Medicine," acknowledges that precision medicine may ultimately make “critical contributions to a narrow set of conditions that are primarily genetically determined.” Yet, they argue, “the challenge we face to improve population health does not involve the frontiers of science and molecular biology. It entails development of the vision and willingness to address certain persistent social realities.”
In that spirit, we may want to ask whether, in this time of unprecedented social and economic inequality, investors and governments are getting hyped into funding marginally relevant treatments for rare conditions rather than allocating adequate funds to tackle problems that systemically impact health status in America: lack of nutrition, lack of housing, lack of basic healthcare access.
We may also reasonably inquire whether $120 million will buy CRISPR researchers and the media a pass on considering the serious ethical, social, and political concerns that CRISPR poses.
Maggie was diagnosed with Stage IV Invasive Ductal Carcinoma, a breast cancer, at the age of 32. Her risk factors were minimal: she was young, healthy, had never had children, and had no family history of cancer. But Maggie had undergone egg retrieval ten times in as many years because, she said, she wanted “to help people.” She now believes that these procedures caused her cancer.
At the time, Maggie was excited to have her eggs “chosen” by an infertile couple. But over the course of the decade, she gradually became “uncomfortable” with the fertility industry. One turning point came when a nurse urged Maggie to demand more money for her eggs, because of “what you’re going through and how many times he [the fertility doctor] has used you and everything he’s gotten from you.” When a second fertility clinic recruited her because of her previous successful egg retrievals, she felt it was a bit odd. She became more suspicious when a fertility clinic discovered a lump in her breast, but then declared it to merely a cyst. Months later, a doctor unaffiliated with the fertility industry diagnosed her Stage IV breast cancer. Looking back, she notes that one of the fertility clinics also excised precancerous cells from her cervix, but didn’t mention the association between hormone treatments and cancer.
Like many other women who provide eggs for other people’s fertility treatments, Maggie didn’t know that long-term studies of the effects of egg extraction are lacking, and that therefore caution should prevail. We do know, however, that short-term risks include ovarian hyperstimulation syndrome (OHSS), with symptoms including abdominal pain, vomiting, and shortness of breath . Other risks include infection, damage to ovaries, infertility, and of course breast, ovarian, or endometrial cancers. Studies about the incidence of these problems have found widely varying rates.
In addition to the disturbing inadequacy of research about egg retrieval, there is also a dearth of regulation of the fertility industry. That fertility clinics performed ten egg retrieval procedures in Maggie’s case is an example of the consequences. While the fertility industry’s own professional organizations – the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technologies (SART) – recommend no more than six cycles of hormonal treatment for IVF and/or egg retrieval, Maggie nonetheless underwent ten.
Is Maggie’s experience an outlier? How many other egg providers have stories similar to hers? How many contract cancer, and how do those rates compare to women who haven’t had their eggs harvested? Until we have better research, tracking, and regulation of egg provision and the fertility industry as a whole, these important questions will remain dangerously unanswered.
Posted by Nathaniel Comfort, Biopolitical Times guest contributor on August 12th, 2015
"Get out of the way." So said the European colonists as they pushed indigenous Africans, Americans, Aborigines, and Maoris off their own lands to make way for Christianity, urbanization, Western medicine, industry, capitalism, railroads, and global warming. And so says Dr. Pinker on behalf of biomedicine, stating what, in his view, should be the "primary moral goal" for bioethics.
"Biomedical research," he writes, "promises vast increases in life, health, and flourishing." To him, ethics is but a horsefly dogging the progress of the potent, muscular thoroughbred of biomedicine—an annoying obstacle bogging down life-saving research in "red tape, moratoria, or threats of prosecution based on nebulous but sweeping principles such as 'dignity,' 'sacredness,' or 'social justice.'" If he and other scientific cheerleaders had their way, not only regulation of medical research but even serious discussion weighing potential harms and benefits would vanish, so that the researchers could get on with their task of saving the world.
Pinker's Panglossian paean notwithstanding, biomedicine, like industrialization, has a mixed legacy. Industrialization has brought improvements in public health and quality of life, reduction of death and suffering, and profound creativity and culture. But it has also led to the destruction of cultures and ecosystems, pollution, and climate change. Further, it has increased some forms of suffering—through, for example, sweatshops, child labor, and occupational disease and injury. Industrialists, too, like to cry "Get out of the way!" to regulators who think beyond the short term.
In support of his argument Pinker invokes nebulous but sweeping principles such as health, flourishing, suffering, disability, harm, and effective treatment—all terms with real but complex meanings that shift with time, context, and geography. A few decades ago, biomedicine considered homosexuality a mental disorder demanding treatment; today such a view is a barbarism. Until the 1970s, deafness was considered a severe disability demanding segregation and rehabilitation; today, the Deaf community has a vibrant and distinctive culture and genetic counselors sometimes help deaf couples increase their chances of having a deaf child.
And of course, the mother of all examples—the root of modern bioethics—is the Nuremberg trials, in which distinguished German physicians were charged with war crimes for carrying out unfettered human experimentation. With all ethical principles pushed out of the way, Nazi doctors were free to subject their "patients" to atrocities, often carefully controlled and carried out according to established principles of the scientific method—but against all norms of humanity.
But one need not Godwin the discussion to find examples of the value of regulation and ethical discussion of biomedical research. When ethicists got in the way, the decades-long Tuskegee study of untreated syphilis was finally halted, in 1972. When the historian Susan Reverby got in the way in 2010, she unearthed evidence of the deliberate infection of Guatemalans with syphilis and gonorrhea in the 1940s. When regulators got in the way in 2000, retroviral gene therapy experiments were temporarily halted, reining in the biomedical cowboys and doubtless saving the lives of patients like Jesse Gelsinger, the teenager who died mysteriously in a routine gene therapy experiment. When ethical discussion got in the way, William Halsted's radical mastectomy procedure for breast cancer—a life-saving, state-of-the-art technique in the early 1900s—was scaled back, preserving much more of the patient's tissue without sacrificing survivorship. When ethical discussion got in the way, the use of sentient animals such as chimpanzees and dogs in vivisection experiments was reduced or eliminated.
There's no denying that biomedicine has brought about many benefits to society. Even if its contributions were limited to antibiotics and anaesthesia, it would be a heroic, potent, and noble discipline. But with great power comes the potential for abuse. Biomedicine's promise for reducing suffering and improving our lives can only be maximized if research takes place in a context of reflection, deliberation, and regulation. Thinking these complex issues through takes time, and impatient researchers may become frustrated at times. Fidget away, Dr. Pinker.
Humanistic debate can help identify potential harm in research practice: critical ethicists and historians deliberately get in harm’s way to spare harm to others. The more powerful biomedicine becomes, the more we need critical discourse to keep its technical advances in humane perspective.
Dorothy Rice Peirce in 1916. Source: Wikimedia Commons
[Forgotten Stories of the Eugenic Age is a blog series exploring the lesser-known ways that eugenics affected and engaged American lives during the first half of the twentieth century.]
The previous installment of this series reviewed the early twentieth-century idea that eugenics could be a tool for selecting a good spouse and building a happy marriage. The optimistic eugenists promoting this approach might not have expected that eugenics could also play a role in the demise of romantic relationships.
Though divorce was difficult and stigmatized in the early 1900s, about 10 to 15 percent of American marriages were legally ended between 1910 and 1925. Judges typically only granted divorces for abandonment, adultery, or abuse. Perhaps because marriages were so often permanent, a woman could sue a man for damages if he ended an engagement to marry. (The reverse was rarely true, since it was considered a woman’s prerogative to change her mind.) Eugenics featured in several “breach of promise” cases because it was a convenient and seemingly moral reason for a man to “cry off.”
In the most high-profile and dramatic of these cases, covered by the Washington Post in 1916, Sigma Ahlgren sued Ward Hall Ream for $10,000 for ending their engagement. Ream had reneged on his promise to marry Ahlgren when her doctor, Lucetta Morden, diagnosed her with tuberculosis, a disease many believed was inheritable. Although Ream affirmed that Ahlgren was a “respectable young woman,” he claimed she didn’t meet his “ideal of a mother.” Ahlgren denied that she was tubercular and argued that she had since obtained two physicians’ certificates indicating that she was “a magnificent specimen of womanhood.” She further declared that she would be willing to “‘prove it in open court,’ if the judge wants her to.” (The Washington Post article notes sardonically, “The judge doesn’t.”)
Ahlgren offered an alternative reason for Dr. Morden’s diagnosis: a nasty love triangle. She accused Morden, Ream’s longtime family friend, of being a “catty” rival for his affections. Morden denied that she harbored romantic feelings for Ream, only admitting to a “friendly interest.” The court hearing eventually fell into disorder, with Ahlgren and Morden sniping at each other about their age and physical appearance.
In a similar breach of promise case, Rose Markewsky brought a $25,000 suit against Charles F. Drucker after he broke off their engagement. Drucker alleged that he ended their engagement when he discovered that Markewsky's brother had tuberculosis. Markewsky refuted this accusation, adding that her brother “is a stronger man than Mr. Drucker.” She continued, “I might have been entitled to break the engagement from a eugenic standpoint, but certainly Drucker was not. I can play better golf and tennis than he can today. I was never ill a day in my life.”
In yet another case, David Arthur Greenhouse of New Jersey ended his engagement with Bertha Schechtel when she told him that she was infertile. Schechtel sued for breach of promise, but the judge found for Greenhouse, declaring that a man had a right to children, children had a right to "a heritage of mental and physical health," and matrimony "concerns the entire human race." The judge said, "A man or a woman is justified in withdrawing from a marriage contract if he finds that his, or her, prospective life partner has a sufficiently serious physical or mental defect.”
If publicly labeling one’s former romantic partner as biologically inadequate appears cruel, perhaps even more striking than the breach of promise cases are the dissolution of eugenic marriages. In 1914, the Washington Post highlighted the story Josephine and Joseph Sanger of Cleveland, each of whom hurried to beat the other to the local courthouse to file for an annulment of their eugenic marriage. In their suits, each alleged that the other had “misrepresented [his or her] physical condition.” Said Mrs. Sanger, “He told me he was a marriageable, healthy man. I found out he wasn’t.”
Yet another eugenic marriage unraveled after only one month. Both Mr. and Mrs. Perron had obtained eugenic health certificates and both had “declared that their mating was in strict accord with scientific principles.” But after only a few weeks of marriage, the groom told police that he had been assaulted by a man whom he had encountered alone with his wife. In her defense, the bride complained that all of the eugenic praise had inflated her husband's ego.
Though all these stories about the termination of eugenic marriages made news, the public was particularly shocked by the divorce of Waldo and Dorothy Rice Peirce.* Waldo was a former Harvard football star, World War I ambulance driver, and rising painter. Dorothy was a millionaire heiress and famous aviatrix who had trained women war pilots. While there is no evidence that Waldo and Dorothy regarded their marriage as a “eugenic” one, many others saw it that way. Waldo and Dorothy seemed like the perfect couple, and in accordance with eugenic principles and eugenists’ promises, their marriage ought to have been a happy one. Nonetheless, the New York Times reported in 1917 that Dorothy filed for divorce from Waldo on grounds of non-support and cruel and abusive treatment.
Newspaper stories grappled with the question of how a relationship between two such perfect—even eugenic—individuals could fail. The December 9, 1917, issue of the San Francisco Chronicle included a full page spread on Dorothy and Waldo’s divorce with photographs of the unhappy couple, entitled “The Sad and Very Imperfect Romance of a Perfect Man and Perfect Woman.” The article stated that when Dorothy and Waldo married in 1912, the public saw it as “the test of a new biological theory—the mating of two perfect persons.” It continued:
The young couple were hailed as the progenitors of a new race: exponents of the theory that only the perfect man and the perfect woman should be allowed to marry. Scientists, surgeons and medical men, educators and ministers, legislators and sociological theorists, witnessed the marriage with great expectancy, hoping it would prove and that the children that should come of it would prove the contention that eugenic principles and not the impulses of the heart should be the foundation of every marriage license.
But now, the perfect man and the perfect woman “declare that perfection, like familiarity, breeds contempt.”
The article attributed to Dorothy the claim that her husband was violent because of his pride in his physical perfection and to Waldo the accusation that Dorothy's bohemian eugenic upbringing, fashioned by her mother to mold her into the "perfect woman," had skewed her marital expectations. Although Waldo had passed the eugenic tests upon which Dorothy's mother had insisted, their marriage had not lasted. How could perfection have gone so wrong?
From our twenty-first century vantage, perhaps a better question is why the public was so surprised, and how twentieth-century Americans so easily accepted eugenic claims about perfection. It seems fairly obvious that expectations of flawlessness are rarely met by fallible people in a complicated world. And a close look at the intricate social effects of historical eugenics reveals that just as the label of "defective" can do harm—in the cases of individuals sterilized and institutionalized, or, more simply, in promises broken—so can the label of "perfection." Treating individuals not as complex human beings with intrinsic worth but as gradations on some arbitrary "quality" scale not only hurts those who do not rate highly, but places unrealistic expectations on those who do. The greater the external pressures for perfection, the more profound the sorrow, disappointment, and shame when we inevitably fall short. This pain is even more acute when the pressures emanate from those who have promised to love us.
After Dorothy Peirce's marriage ended, her "heartbroken" mother said, "I had hoped my daughter would be honored in all future histories of the world as the creator of the perfect race. I am sorry she could not become more than a mere wife—and an unhappy one at that.”
For her part, Dorothy pledged, "I want no more perfect men. My next husband will have been examined most carefully before we approach the altar, not for perfection, but for signs of the faults that will make him human.”
*Some sources incorrectly spell their surname as "Pierce."
1. “Aviatrix Seeks Divorce.” New York Times, Oct. 16, 1917.
2. “Eugenics and Law in Charge to Jury.” New York Times, Dec. 18, 1914.
3. “Eugenics Breach of Promise Suit Due to ‘Catty’ Rival, Declares Girl.” Washington Post, Feb. 27, 1916.
4. “Eugenic Bride Packs Up Her Belongings.” Boston Daily Globe, Jul. 29, 1913.
5. “Failure in Eugenics." Washington Post, Aug. 24, 1913.
6. “Girl Says Eugenics Broke Troth, Sues Man.” St. Louis Post-Dispatch, Aug. 29, 1913.
7. “History in the Making: First Eugenic Marriage Is Failure.” San Francisco Chronicle, Aug. 17, 1913.
8. “Jilted by Eugenic Wooer.” Washington Post, Feb. 26, 1916.
9. Jones, Audra M. “Historical Divorce Rate Statistics.” Accessed August 5, 2015. http://divorce.lovetoknow.com/Historical_Divorce_Rate_Statistics.
10. “The Sad and Very Imperfect Romance of a Perfect Man and Perfect Woman.” San Francisco Chronicle, Dec. 9, 1917.