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Tonight I ask you to pass legislation to prohibit the most egregious abuses of medical research: human cloning in all its forms ... Human life is a gift from our Creator — and that gift should never be discarded, devalued or put up for sale. –George Bush, State of the Union Address, January 31, 2006 (1)
Stem cells and IVF research
THE PRESIDENT’S HOSTILITY to research involving human zygotes has a long history. A generation ago, in 1971, Dr. Leon Kass anticipated Mr. Bush in a polemic against IVF entitled "Babies by means of in vitro fertilization: unethical experiments on the unborn?" Kass raised the banner of bioethics against assisted reproduction and defined a rigid notion of the origin of life. (2)
In turn, Kass’s question was posed by the devout at the dawn of the 20th century, when Jacques Loeb at the Marine Biological Laboratory succeeded in activating a sea urchin egg in vitro: what price for life in a dish of salt water? The New York Times downplayed "Dr. Loeb’s Incredible Discovery," calling it "very interesting but not especially important, [since it] will not revolutionize our concepts of the origin of life" (3)
.
But Loeb’s sea urchin experiments became the basis of modern developmental biology both in the lab (think of cell cycles and cyclins) and in the clinic (think of Louise Brown, the world’s first IVF baby, now 27 years old). Meanwhile, Dr. Kass went on to chair President Bush’s Council on Bioethics from 2001 to 2005. Undaunted by the worldwide success of IVF, and the thousands of families it has fulfilled, Dr. Kass raised the banner of bioethics again, this time after his Council’s split decision on human stem cell research (hES). In concert with Congress and the administration, Kass and his Council have essentially scotched support for hES research by the federal government. Their stance has won strong support from The National Review and the Discovery Institute, an organization devoted to beating up on Charles Darwin by teaching intelligent design in the schools (4)
.
Swept by the tide of what Kevin Phillips has called the American Theocracy, with its "rising commitment to faith as opposed to reason and a corollary downplaying of science," (5)
the Bush administration has restricted hES studies to a few unpromising cell lines established before August 9, 2001. Happily, individual states and private entities have assumed the task of new human stem cell research; but until recently, the United States lacked a national set of standards—an ethical guide to the science, the hazards and the promise of hES.
ESCROCs
With courage and foresight, the National Academy responded to this need, and in April of 2005 issued its own "Guidelines for Human Embryonic Stem Cell Research" under the aegis of the National Research Council (NRC) Board on Life Sciences and the Instititue of Medicine (IOM) Board on Health Sciences Policy (6)
. The NRC/IOM "Guidelines" deserve the support of everyone in science. This concise, yet definitive, 166 page document was drafted by an impeccable cast of scientists, lawyers, and clinicians: it constitutes a noble attempt to merge meliorist science with the temper of our time. In keeping with the model of DNA regulation by RACs (Recombinant DNA Advisory Committees), the "Guidelines" sensibly called for letting a thousand oversight committees bloom, one for every institution that plans to conduct hES research. Other suggestions included a review of the procurement process, provisions for the banking of cell lines, assurance of informed consent, adherence to standards of clinical care, etc.—the document should serve for years to come as a guide to conduct and action.
One minor quibble: someone must have had a tin ear to propose the acronym ESCRO (Embryonic Stem Cell Research Oversight) for the local oversight bodies—ought we to pronounce the word "escrow," as in secure deposit? Worse yet, the complete acronym, ESCROC, should amuse anyone conversant with French: ESCROC means crook, as in a Le Monde headline of 1973: "Richard Nixon: Je ne suis pas un escroc!" (7)
.
But the awkward acronym is not the most puzzling aspect of ESCROCs—the restricted composition of their National Advisory committee is more of a problem. This spring, the NRC/IOM requested nominations for a super ESCROC to provide oversight of research with human embryonic stem cells (8)
. The "Guidelines" propose that "a national body should be established to assess periodically the adequacy of the policies and guidelines proposed in this document" (6)
. In keeping with the charge of its parent body, the call for nominations to the Advisory Committee carries the warning: "Please note that individuals conducting research using human embryonic stem cell will not be eligible (animal and adult stem cell researchers will be considered)." That exclusion seems to carry undertones of the president’s 2006 State of the Union Address, or of Dr. Kass’s 1971 warning against "unethical experiments on the unborn." One notes that Dr. Kass has remained as adamant as his President, testily reminding Nicholas Wade in 2005 of the party line on stem cells: "Congress is still on record as saying, ‘federal funds may not be used in research in which human embryos are harmed or destroyed’ "(9)
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As a private body, the NRC has every right to pick whomever it wants for its Advisory Council; and judging from the group that put together the "Guidelines" we can be assured of a concert-grade ensemble. Moreover, the staff has insisted that the exclusion of researchers who are actually working on hECs was by no means due to political pressure. The exclusion is in place, we are assured, "simply to avoid the conflict of interest that would arise if researchers working with human embryonic stem cells were to write the rules governing their own activities." (8)
That argument isn’t entirely persuasive, for at least two reasons that come immediately to mind: first, the RAC’s are populated by scientists who are themselves engaged in recombinant DNA research; and second, while there is no federal oversight body for IVF, its policy and practice are monitored by active members of the Society for Assisted Reproductive Technology (SART). Its members see no conflict of interest between performing IVF themselves and the task of "setting and promoting the standards for the practice of assisted reproductive technology" (10)
. No, I’m afraid that the Academy’s exclusion policy is a well-meaning display of caution and compromise in the face of implacable foes. A Freudian might call it a collective "introjection of the aggressor." I’m reminded that Jacques Loeb faced similar problems a century ago.
Loeb and in vitro fertilization
Each June I pass through a building named after Loeb at the Marine Biological Laboratory at Woods Hole, where reproductive biology has flourished since 1888. In 1900, Jacques Loeb was accused of transgressing the limits of science when he first produced viable sea urchin larvae by means of parthenogenesis (11)
. Accusations flowed: fatherless babies violated natural law, divine intent had been breached, and Loeb was charged with proposing the "atheistic hypothesis" that life had a physico-chemical origin. He had, after all, created a form of new life in a dish. Loeb tried to calm the waters, perhaps in the same spirit of reasonable compromise shown by the NRC/IOM today: Loeb disclaimed in 1900 that "The experiments are not far enough developed to arrive at any definite conclusion regarding this subject, and I do not know how far we shall be able to go in the work of artificial production of life." (12)
In the same vein, Loeb’s colleague at the MBL, F. R. Lillie, assured a local newspaper that the creation of vertebrate embryos in vitro was a very long way off: "Why, it would be like finding the North Pole," he explained (13)
. Admiral Peary found the North Pole nine years later.
Loeb also had his supporters. It was as clear to them in 1900, as to us today, that the main opposition to research on embryos in vitro came from "religious sources, where it is recognized that the general acceptance of this [materialist] hypothesis would overthrow the main doctrine, of an infinite all-powerful deity or creator, who has breathed the breath of life into every living thing." (14)
Eventually, Loeb roused sufficient courage to answer a Jesuit critic that "one cannot overlook the fact that the steady progress of science dates from the day when Galileo freed science from the yoke of sterile scholastic methods." (15)
And sure enough, on September 25th, 1912, The Chicago Daily Tribune announced that "PROF LOEB HAS FATHERLESS FROG: Former Chicagoan Exhibits at Hygienic Congress Parentless Animal He Grew." The reporter chuckled in print that "by proper use of chemicals Prof Loeb was able to develop a mature frog, but alas, the professor, so learned in biology and chemistry did not know that a frog could not live in water and he let the poor thing drown. ‘The next one will live,’ says Prof Loeb, ‘because I will bring him up on dry land’ " (16)
. It did, and the work went on.
From Loeb to Pincus and IVF
By 1935, Gregory Goodwin Pincus (1903–1967), best known as "The Father of the Pill," had worked out techniques for fertilizing mammalian eggs in vitro. An untenured assistant professor at Harvard, he also reported that he had activated rabbit eggs with sperm in vitro, reimplanted them in female rabbits, and obtained viable fetuses. Like Loeb, he was a champion of reductionist science: "Careful investigation of the ovum itself and its homeostatic environment is made possible by the various explantation and transplantation techniques" (17)
. We call it IVF.
The specter of human cloning has haunted the stem cell debate from the beginning. And by 1936, the specter appeared in the form of Gregory Pincus. Appreciating that "Not since Professor Jacques Loeb hatched fatherless sea-urchin larvae ... has so striking a success been achieved," The New York Times warned its readers that Pincus’s work would lead to embryo farms "making ninety-six human beings grow where only one grew before" as predicted in Aldous Huxley’s Brave New World" (18)
. But in the 1930s, there were other specters. In rhetoric that smacked of Father Coughlin’s nativist anti-Semitism, Collier’s magazine published an attack on Pincus that featured an unflattering photo of this "Jersey native" as a cigarette-dangling mad scientist, holding a "fatherless" rabbit under his arm. The writer, J. D. Ratliff, traced Pincus’s "goofy" experiments on in vitro fertilization to the work of "Jacques Loeb, the hugely famous Portugese Jew." Ratliff warned that with IVF "Man’s value would shrink, the mythical land of the Amazons would then come to life. A world where woman would be self-sufficient; man’s value precisely zero" (19)
. It was a popular view, in and out of the academy: Pincus was denied tenure at Harvard.
The fuss over Loeb and Pincus was enough to keep in vitro fertilization under wraps in the United States until 1978 (pace, Landrum Shettles and John Rock). Meanwhile Britain got on with it and gave us Louise Brown: the model of less talk and more action. We’ve now had a replay of those early days of IVF in today’s debate over hES. But, given that history, I’d bet that even our God-fearing lawmakers will prove powerless to stop scientists here and/or abroad from working on "the various explantation and transplantation techniques" (à la Pincus) required to bring human embryonic stem cell research from the dish into the clinic. And, thanks to the meliorist "Guidelines" of the NRC/IOM, the work will have a strong ethical base. One hopes that it will be overseen by an Advisory Committee staffed, in part, by those who’ve worked on human embryonic stem cells in lab and clinic.
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FOOTNOTES
The opinions expressed in editorials, essays, letters to the editor, and other articles comprising the Up Front section are those of the authors and do not necessarily reflect the opinions of FASEB or its constituent societies. The FASEB Journal welcomes all points of view and many voices. We look forward to hearing these in the form of op-ed pieces and/or letters from its readers addressed to journals{at}faseb.org.
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