blog.bioethics.net

Stem Cell Suburbs

We’ve written before about so-called “stem cell suburbs”, traditionally Republican suburban Congressional districts that are more socially liberal than the Republican party’s base. Democrats are mounting unexpectedly strong challenges in many such districts this fall and are pushing hard on support for embryonic stem cell research to appeal to independents and moderate Republicans who are uncomfortable with the national party’s social conservatism.

This article by Jodi Kantor in the New York Times over the weekend profiles another such district— the 8th District in Washington state (suburban Seattle), which is home to a large number of people who work at Microsoft and related technology companies. The district is wealthy, well-educated and economically conservative and has traditionally been a Republican stronghold. While the district narrowly went for Kerry in 2004, it has never elected a Democrat to Congress— Republican Jennifer Dunn represented the district for twelve years and was replaced in 2004 by Republican Dave Reichert, who came to local prominence as the sheriff who caught the Green River Killer.

The current Congressional campaign, however, is rated as a toss-up by most national political gurus. Democratic challenger Darcy Burner, a former Microsoft executive who has no prior political experience, is mounting a strong challenge to Reichert by capitalizing on popular discontent with national Republican positions on a variety of issues, including most prominently embryonic stem cell research. Kantor notes:

“This year, one issue incenses them (engineers and other professionals who live in the district) above all others: restrictions on embryonic stem cell research…It is a matter of concern across the country, even across parties. But for many engineers and their ilk, restriction of stem cell research is what gay marriage is to conservative Christians, a phenomenon so counter to their basic values that they cannot vote for anyone who supports it….for Bellevue (the major town in the district)’s professionals, science is not only a means of creating wealth but also an idealistic pursuit, the most promising way they know of improving the human condition”

Burner, a strong campaigner who has been endorsed by the major Seattle newspaper, has been criticizing Reichert as a strong supporter of the Bush Administration on a wide range of issues from the Iraq war and detention and trial of foreign detainees to global warming and the minimum wage. Reichert, who is well-liked and well funded, opposed the Bush Administration’s position on Terry Schiavo and in fact changed his position on embryonic stem cell research, voting in favor of the bill President Bush vetoed to expand federal research support. It remains to be seen if these positions are sufficient to keep him in office in what seems to be shaping up as a referendum on national political issues.
Jim Fossett
AMBI Federalism and Bioethics

Caplan on Fox Ad

In his MSNBC.com column Art writes:

The TV ad is disturbing and difficult to watch. Michael J. Fox's face, so familiar from all his appearances in the "Back to the Future" movies and hit TV shows such as "Family Ties," "Spin City" and "Boston Legal," bobs uncontrollably around the screen. Why? Then you remember: Fox is a relatively young man who suffers from Parkinson's disease. And that is precisely the point of the ad.

Fox is pushing the voters of Missouri not to forget people like him, who suffer from incurable diseases, when they get to the ballot box in less than two weeks to decide who will be the next senator from Missouri.

It is not surprising that support for embryonic stem cell research is an issue candidates are using to differentiate themselves from their opponents. Polls consistently show the majority of Americans support embryonic stem cell research. What is novel and noteworthy is that the battle to secure public funding for embryonic stem cell research has created a new special interest group that might influence American politics for many years to come: the disease advocacy lobby.

Some on the opposing side of the stem cell issue have a vague inkling of the power of the emerging disease advocacy lobby and it frightens them. Rush Limbaugh, who currently serves as a pro bono Republican National Committee press hack, had a brain freeze when he realized that Fox had decided to come out swinging on stem cells. Rush fumed on his radio show that Fox had clearly gone off his meds to make the ad and that he was "acting."

Now there are people who need to be off their meds - Limbaugh apparently has serious jones for pain pills. But, it is certainly fair to make an ad about the need to for research to cure your disease without trying to cover up your symptoms. What really drove Limbaugh nuts is that he senses that Fox's tremors could really shake up the vote in states such as Missouri.

A constitutional amendment on the Missouri ballot would legalize embryonic stem cell research. Proponents have spent more than $28 million - about 10 times as much as critics - to get the initiative passed. The incumbent senator, Republican Jim Talent, is facing a tough challenge from state auditor Claire McCaskill partly because she is a staunch supporter of embryonic stem cell research and he is not. Ads like Fox's clearly are having an impact.

Another equally tough political ad that rivals the emotional power of the Fox ad is airing in upstate New York in the 25th Congressional District. In it, a mom, a young girl and a teenage boy want to know why Republican Rep. James Walsh voted against federal funding of stem cell research, thereby condemning them - and people like them - to have to struggle with diabetes or paralysis. The stem cell issue is, if not front and center, then at least popping up in congressional races in Illinois, Florida, New Mexico, Pennsylvania, Virginia and other states.

In Maryland, Democratic Rep. Ben Cardin and Republican Lt. Governor Michael Steele, candidates for the open Senate seat, strongly disagree about public funding for embryonic stem cell research. At one point, Steele got in a heap of trouble for comparing embryonic stem cell research to Nazi medical experiments in concentration camps.

In the race for the governorships of Maine, Massachusetts and Wisconsin, democrats are trying to use their party's support for public funding for all forms of stem cell research as a weapon against Republicans.

Political analysts and pundits have noted that the stem cell issue is surfacing in some close races. What the pundits are missing is that the stem cell issue is not just a matter of a tiny interest group pushing its pet agenda. The emerging new interest is not only capable of raising money to support pro-embryonic stem cell research candidates, but perhaps of delivering crucial votes on Nov. 7 and beyond.

Just a few months ago a Republican Congress came very close to overriding the only veto that President Bush ever made - to block public funding of embryonic stem cell research. How did it happen that Congress, which was strongly opposed to such funding back in 2002, and being lobbied hard by the influential pro-life lobby, shifted with a majority supporting public funding in both the House and the Senate by 2006?

The answer has a little to do with the power of ethical arguments in favor of funding embryonic stem cell research to change minds. What Congress really responded to was an incredibly well-organized and powerful lobby of disease and disability organizations. These include those fighting to help people with cancer, diabetes, amyotrophic lateral sclerosis (Lou Gehrig's disease), Parkinson's disease, infertility, paralysis, blindness, heart disease and a variety of other disorders and ailments. For the first time ever, these groups pulled together and made their lobbying presence felt to the point where a Republican Congress came close to abandoning a president from their own party.

Not only do these groups command money, politicians realize they also control votes. If you total up the number of people who have these diseases and disabilities, their families and friends and those who take care of them you are talking about millions and millions of Americans.

In close races around the country this new lobbying group may be capable of getting people to vote and make the difference as to who wins. If you keep an eye on their Web sites, you will see disease advocacy groups in many states organizing to get their members and friends to the polls.

If the coalition that formed so effectively around advocacy for embryonic stem cell research hangs together, it may well become a force that American politicians ignore only at their peril.

Look around at your polling place - if you see more people than usual in wheelchairs, using a cane, walking a bit slowly or being helped into the polling place by a sibling, friend or parent, you may be watching the start of a new phenomenon in American politics.

Wounded Cats

Michael J. Fox and his pro-embryonic stem cell message are apparently turning into a factor in several elections. In addition to the spot supporting Democrat Claire McCaskill in the Missouri Senate race that Glenn [McGee] describes below, Fox has also made similar spots supporting Ben Cardin in the Maryland Senate race and incumbent Jim Doyle in the Wisconsin gubernatorial contest and is making appearances in support of Robert Menendez in the New Jersey Senate race and Tammy Duckworth in the Illinois 6th Congressional District, a race we’ve written about before. Matthew Mosk of the Washington Post describes the Maryland spot and local reaction to it is here.

The wounded cat screeching from stem cell opponents attest to the ad campaign’s effectiveness, the more so because the countercharges being lodged have so little substance. Rather than being “exploited”, Fox appears to be reaching out to campaigns where he thinks his message may have an impact and appears to be doing a good job of identifying the right ones. Apparently, he volunteered. Second, the claims he actually makes for embryonic stem cell research are not overstated. Both the spots themselves and the Website of Fox’s foundation, available here avoid the claims of eminent cures made by some advocates. The word “cure” doesn’t appear in the spots at all. Rather, embryonic stem cell research is described as a promising line of research that gives hope to disease sufferers, which seems about right for this stage of things. The sneering cracks by Rush Limbaugh and fellow bottom dwellers that Fox is “off his meds” or is “acting” appear to be exactly backwards. I’m no neurologist and don’t even play one on TV, but at least one neurologist, as reported here , notes that people with untreated Parkinson’s disease actually frequently appear stiff and frozen and have trouble walking or performing simple motor tasks. The jerky, involuntary movements that make the spots so painful to watch are a commonly reported side effect of levodopa, which is a primary treatment for Parkinson’s, as reported here on the website of the National Institute for Neurological Disorders and Stroke. Fox doesn’t look the way he does because he’s off his meds, but because he’s on them.

Complaints that the ads are self-pitying or in bad taste also miss the mark. To the contrary, the spots owe much of their effectiveness to their understatement. Fox is an effective presenter and the implicit contrast between a straightforward request for support and the obvious effort it’s taking him to make it don’t need embellishment. Claims about the potential benefits of stem cell research may be difficult for most to evaluate, but a personalization of one of the problems that researchers are trying to fix sends a strong message that real people have things at stake in this debate. As advertising, this stuff is hard to beat.
Jim Fossett
AMBI Federalism and Bioethics Initiative

Rush Limbaugh Steps Over the Line

I have always considered most of what Rush Limbaugh has to say a product of either racism (see his comments on Eagles quarterback Donovan McNabb's skills and prominence) or ideology.

Limbaugh has now stepped completely over the line. A man who himself has a drug abuse problem has the gall to accuse Michael J Fox of faking his symptoms to gain sympathy for the stem cell cause. At least when Howard Stern got in trouble on the public airwaves it was due to his juvenile reliance on fart jokes and porno star sound clips to retain his audience. Limbaugh is quite content to lie.
- Art Caplan

Wanted: Director of Graduate Studies

Yet again we find ourselves asking those of you with talent in bioethics to ask yourself the question everyone has on the tip of their tongue: exactly how cold does it have to be before my nose falls off? do I want to move to Albany to work in bioethics.

The Alden March Bioethics Institute is looking for a Director of Graduate Studies to lead new graduate programs, all of which will involve really, really innovative teaching technology, like megaphones the use of portable digital audio and video, synchronous conversations with faculty, internships that involve remote participation in key meetings in cutting edge research facilities, or even in ethics case discussions. This is in addition to the great positions just announced in the philosophy program at University at Albany. With this position, our goal is to do for online bioethics education what we've done for our coffee bill since they opened a drive-through Starbucks on the way to the medical center bioethics publishing, namely increase accessibility, rigor and impact by using cutting (but not bleeding) edge technology that makes the "computer part" easier to use, and increases the amount of "face time" with leaders in bioethics, and provides more direct mentoring than any masters program, online or off. Of course, first all of this stuff has to be approved by New York State, but we've skipped sleeping to try our best to make sure that happens, and in time for students to join our new program in fall 2007 (meanwhile, our other Masters program continues, while not admitting new students at this time).

If you have teaching skills, mentoring that has paid off for your students, a real sense of the relationship between the research activity in a large (and growing) bioethics program and the teaching activities of such a program, tell us and maybe you too can spend $150 a month on coffee join the energetic team that produces AJOB, edits two book series, participates in federally and foundation research current funded in excess of $2.5 million, and ... well you get the idea, or if you don't, check out the ad and the website. But yes it does snow three or four months a year. Not like Buffalo, but more than Texas. Beach bums need not apply.

Hard to watch. Powerful.

I guess if you can spend this much money on a campaign with stem cells at the center, you can get an ad like this together. But this ad may well foreshadow the next presidential election. Joshua Marshall noted in his Talking Points Memo that the thing is still too close to call (well that wasn't his metaphor, but I didn't like his metaphor. But the ad is precisely what will turn the tides against the Rove move to turn social issues into a "get out the church vote" in key swing states. Maybe.

At a minimum it returns the tone of the debate to the Star Versus Star model, where you'll recall (well, I do anyway, because I had to debate him) that Mel Gibson was the best that the "other side" could do - and he's begun to demonstrate that his hard line position may be a symptom of near-psychosis perhaps a less effective "star representative." There are always the Snow Children, I guess.

What is so troubling about these commercials, as with the Reeve commercials, is that they plainly foment therapeutic misconception: people in Missouri should not have to believe that Mr. Fox would be cured if only the President had funded stem cell research, or that Missouri could somehow do much much more than its current, formidable stem cell research were there a little bolus of cash in that state for the science. It's not as bad as right wing ads that flat out lie about adult stem cell "therapies," or signing ceremonies with a few of the miniscule number of embryos ever to be adopted - none of whom were destined for stem cell research anyway. The ad is above

Wall to Wall Cash in Missouri:
The Next Step in Federalism in Stem Cell Research is Big Bucks

This article by Matt Franck in Monday’s St. Louis Post Dispatch notes the large amount of money being spent in support of the Missouri constitutional amendment to unambiguously legalize embryonic stem cell research in that state. To date, Franck reports that pro-amendment forces have raised $28.7 million, or more than has been spent by all candidates combined in any statewide race to date in Missouri. Anti-amendment forces have raised far less—something less than $2 million to date.

What’s particularly interesting is that almost all the spending in support of the amendment has come from one couple---Jim and Virginia Stowers, the founders of the American Century family of mutual funds. The Stowers have also donated over $1.5 billion to found and support the Stowers Institute, a first class medical research center In Kansas City that is heavily involved in stem cell research. In addition to supporting the amendment, the Stowers have also put a major planned expansion of the Institute on hold pending the outcome of the amendment vote.

Predictably, amendment opponents have been crying foul, claiming that such hefty financial contributions have distorted the electoral process (one doubts that they would turn down donations of that size). It’s worth noting, however, that such issues have come up before, in the debate over Proposition 71 in California, which created that state’s embryonic stem cell research initiative. Prop 71 was largely the brain child of Robert Klein, a wealthy real estate developer who contributed $3 million of his own money (out of $25 million spent) on the campaign to pass the proposition. Klein wrote a job for himself into the proposition, prompting accusations that he was using his money to bypass the normal political process and give control of a large amount of public money essentially to himself without any accountability. Klein has also been able to tap other wealthy individuals for loans and contributions to CIRM (the California agency that manages the stem cell initiative) and others have donated money to California universities and research institutes for stem cell related purposes—one estimate by the Wall Street Journal puts the total private support for stem cells in California at over $100 million.

There are huge amounts of money at stake in the embryonic stem cell research debate, and much of the political and financial support for such initiatives is coming from parties that expect to get something out of them—large research grants, potentially lucrative patents and commercial opportunities, scientific prestige, political credit and campaign contributions, tax revenue and jobs. Bioethicists also have a dog in this fight—CIRM’s draft strategic plan earmarks $25 million to examine the social, ethical, etc implications of stem cell research, and there have been complaints from some quarters that this isn’t enough. By the rules that govern politics and the markets, this is absolutely ok. The right to petition the government for a redress of grievances is enshrined in the Constitution, and capitalism relies on rewards to those who provide society with useful things. The desire for money and status is perfectly compatible with, and is frequently accompanied by, a deeply felt desire to do good and heal the sick. Those who find the scramble for money distasteful might usefully contemplate Adam Smith—“It is not by the butcher’s altruism, but by his avarice, that we may expect to receive our dinner.”
- Jim Fossett, AMBI/Rockefeller Institute States and Bioethics Program

Sizeism

Science Blog, the most read science blog, is running a nutty post that argues that nanotechnology should be assessed in virtue of being small - that small is an exceptional category for the purposes of the FDA. The effect has been huge and immediate, a bit like watching an electronic version of the famous Cambridge, Massachusetts protests against genetic research. It strikes me as incredibly concerning that nanotechnology is already so feared per se by so many on such flimsy evidence.

The Tuskegee University Bioethics Center Opens ... with Lilly Money

Tuskegee University formally opened its bioethics center, led by Vanessa Gamble and established in 1999:

The Bioethics Center, formerly known as the John Andrews Building, underwent a $24-million renovation and reconstruction. With contributions from the National Institutes of Health, the U.S. Department of Health and Human Services, the Centers for Disease Control and Prevention, the Ford Foundation and the Eli Lilly Endowment, the facility, first erected in 1913, stands as a jewel on the campus of Tuskegee University.

"This occasion is excellent in bringing people together to recognize this travesty that occurred within U.S. health care, and it reminds us of what the study meant so many people across the world," says Dr. Leila Willis Frank.

Dr. Frank's father Wilbur Willis, Sr., was among the 400 or so men who went untreated as a result of the government study. He died in July 11, 1970. "I'm happy to be here today to see the rededication to the lives of so many that have come behind those that have participated in the study to better our lives and to understand what health care is and what studies mean," she says.

So here is a truly difficult moment for those who object to any involvement of pharma money in bioethics. In "Pharma Buys a Conscience," one of Carl Elliot's bakers dozen of numbingly parallel articles about the evils of pharma money in bioethics, he argues that Lilly is, um, the root of all evil.

His argument, smashed to tiny bits by James Coyne in a debate and in what might well be the clearest repudiation ever of Elliot's endless arguments that Lilly went after the Hastings Center in illicit revenge against Elliot and David Healy, is still oft cited by those who just don't care that he had all the facts wrong.

So what now will those who oppose Lilly's funding of anything related to ethics say of Lilly's support of the Clinton-initiated program, an amazing program, at Tuskegee? I can easily see the criticisms, for Lilly has indeed taken hits for its 'difficulties' in developing a research ethics program, difficulties that resulted in maybe the most inhumane clinical research facility since Tuskegee (noted in The Wall Street Journal in 1996 in a landmark article I forever find myself citing, when I am ranting that new clinical trials are at least as bad as Tuskegee, i.e., that we seem to have learned nothing about the danger of ignoring bad human subjects research practices).

But Lilly's not holding trials at TU, nor in Macon County, and indeed there is every evidence that the Center is very careful in how it allocates and procures funding. So: calling acolytes of the "pharma money is killing bioethics" crowd: what say you of the creation of an outstanding new bioethics program with the aid of money from a foundation paid for in part by pharma. Lean back in the chair in your medical center office (in the building paid for by drug trials) and ruminate on that.

Transparency in Home (Direct to Consumer) Genetic Testing: Of Cloned Cats and Fetal Sex Predictors

Contributing Editor Ricki Lewis has been looking hard at direct to consumer genetic testing. And cloned cats.:

It was with mixed feelings that I learned of the demise of Genetic Savings & Clone, the Sausalito, CA company that was "the world's leader in the cloning of exceptional pets", as if every strip mall has such an outlet. Founded in 2000 by a billionaire seeking to clone his beloved Missy, of humble mongrel origins, the company intended to eventually clone other members of Canis familiaris for $100,000, and Felis familiaris for $50,000. They succeeded with cats, with a recent price reduction to drum up business.

Animal rights activists protested pet cloning, but a less publicized aim made sense to me - funding research that uses animal embryos at Texas A&M University. If a billionaire's desire to recreate his mutt could support basic research, that's ok, for such research has shed light on causes of recurrent pregnancy loss in humans, among other things. (For the record, I own 6 cats of the uncloned variety, and look forward to being an old crone with 83 of the creatures someday, the more genetically diverse, the better.)

The saga of the recent demise of another genetics-based company offering a direct-to-consumer (DTC) service had more serious repercussions. The saga of Baby Gender Mentor provides a case study of how consumers can be deceived by lists of relevant-sounding scientific articles paired with outrageous claims. It is yet another example of the need for regulation of DTC testing. The emerging buzzword is transparency -- to consumer and health care professional alike as to what exactly a test is testing, and what it means (Lewis).

"Gender Disappointment"

"When I was a resident, the first question in the delivery room was 'is it a boy or a girl?' Nowadays people know that." So began a riveting talk by Diana Bianchi, professor of pediatrics, obstetrics, and gynecology at Tufts University, at the annual meeting of the American Society of Human Genetics in New Orleans October 8-13. Bianchi was referring to the routine use of ultrasound and prenatal tests that reveal fetal gender. She is one of the pioneers of the technology of separating cell-free fetal (cff) DNA from the maternal circulation for use in probing for telltale sequences - such as the SRY gene that heralds a Y chromosome and mutations that cause inherited disease.

Detecting cff DNA grew out of the observation that it's common for a few fetal cells to persist in a woman's circulation, even when that fetus has passed voting age. Sometimes a woman's immune system tunes into those stowaway cells in middle age, causing what looks like an autoimmune attack. As long ago as 1893, doctors reported finding placental cells in the lungs of women who had died while pregnant. Then in 1969, researchers detected Y chromosomes in the nuclei of white blood cells circulating in pregnant women. A 1977 study identified fetal blood cells in 40 to 70 percent of a large sample of pregnant women by the third trimester. In the 1990s Dennis Lo, now at the Chinese University of Hong Kong, and his colleagues took the field in a different direction by amplifying SRY in the maternal circulation - free of cells and not even wrapped up into chromosomes -- and estimated that 3-6% of such DNA in a pregnant woman's plasma is from the fetus (Lo).

Spotting SRY in a mom-to-be's blood is valuable information, because the only way she could be harboring such a macho gene is if she's also harboring a son. By inference, if SRY isn't there, and the pregnancy test strip says "yes", she's carrying a girl. That SRY is a powerful gene, because gender selection is a big market, from individual families wishing to end a string of same-sex births, to entire societies where the fair sex is disappearing (Bhat). The website www.in-gender.com, which is a guide to methods of upping the odds of conceiving, detecting, or banishing an XX or an XY, has a heading for "gender disappointment", with several links to support groups for those enduring this tragedy.

An at-home test called Baby Gender Mentor, from Acu-Gen Biolab, Inc. of Lowell, Mass., offered a test that can purportedly tell gender as early as the 5th week of pregnancy. It cost $25 to submit a blood sample, and $250 to have it processed in a laboratory. The company's website (BabyGenderMentor.com, although the test is unavailable for now) has an impressive bibliography. But like the publication lists at nutrigenetics websites, this one requires some reading-between-the-lines to figure out what the company is actually offering, and how the test has fared as a DTC product. None of the references by themselves validate the Baby Gender Mentor test, but a consumer not accustomed to reading Clinical Chemistry might assume the jargon sounds about right and that the test has passed muster in clinical trials. The situation is about as transparent as mud.

The Acu-Gen website lists 42 scientific papers and patents, most of which detail nuances of PCR, such as blocking repeats to ensure that one is hauling out unique DNA sequences. One paper addresses Y-specific sequences, 3 address cff DNA, and 3 combine the topics, discussing use of PCR to amplify some of that lovely cff DNA. Since Acu-Gen is offering results on samples from weeks 5 through 8, they aren't even targeting fetal material, but embryonic material. But forget Bio 101 for now. I tried to infer just what the heck their test amplifies, which was a little like playing a game of Clue.

My first tip came from the wording that consistently refers to "fetal genetic materials". The plural had to mean RNA, the only other nucleic acid besides DNA. It turns out that two tests are performed on each sample. This is probably because in the absence of the telltale SRY, a daughter's DNA would look just like mom's, unless some marker of embryonic or fetal existence is probed too. Tip #2: what's a gene that's expressed only in an embryo or fetus? My best guess: embryonic or fetal hemoglobin. Haul out some epsilon or gamma globin chains, and you've got a lurking embryo or fetus. (Theoretically one could test for a gene variant known to come only from the father, but that would be much too labor-intensive and not always informative, especially if mom and dad are from the same ethnic group.) What Baby Gender Mentor actually tests for is proprietary, and the company claims it hasn't published clinical trial data because they are awaiting patent protection (Kaiser 2005). So stay tuned.

What drew attention to Baby Gender Mentor, both to consumers and scientists, wasn't the list of publications, but rather the unscientific-sounding claims. In earlier renditions of the website, before mistakes started cropping up, the company claimed 99.9% accuracy, and that they offered a test "superior to any other gender test on the market" - which Bianchi pointed out was news to geneticists. Most convincing to consumers was the offer of a 200% return on one's investment should appearance at birth contradict the company's prediction of gender. It was, I think, a smart marketing strategy: simply charge enough to offset the payback for any errors, all the while creating an aura of confidence. Many fell for it. But then the publicity backfired.

First came a spot on the Today Show that, while perhaps not as offensive as the "who's the daddy" reveals on Jerry Springer, was still an entrant in the bad taste hall of fame. A pregnant woman with two daughters had the gender of her third child-to-be revealed on air by a company representative. The verdict - yet another XX - was greeted with a glum "another one" from the woman, before she muttered a subdued "a third is great" (Kaiser 2005). Newspapers, NPR, and local TV and radio stations picked up the story. More distressing was an ABC Action News in Tampa Florida report on a woman whose husband was serving in Afghanistan. She was told the fetus had a lethal extra chromosome 18, detectable somehow by her sample having excess DNA. The child was born healthy. Then cases began to accrue of ultrasounds inconsistent with Baby Gender Mentor predictions. This led to women undergoing the risk of invasive prenatal diagnosis procedures to straighten the contradiction out.

Bianchi, a vocal supporter of regulation of DTC genetic tests, wasn't surprised as the mismatches began to accumulate, because studies that she had participated in and were listed in the Acu-Gen bibliography had shown that detecting cff DNA is not nearly as far along as Acu-Gen would have a consumer believe, with their claims of "unsurpassed sensitivity." In that study, samples from 20 women 10-20 weeks pregnant were divided in 5, and sent to 5 different labs for analysis of total DNA and presence of SRY (Johnson). All but 4 of the 100 samples were assigned the correct gender - not quite the 99.9% that Acu-Gen claimed. Acu-Gen's technique, whatever that might be, would be expected to be even less accurate because levels of embryonic cell-free DNA are lower than fetal levels.

The latest incarnation of Acu-Gen's website oozes disclaimers, yet still reads "The test is able to identify the presence of fetal genetic materials often as early as five weeks after conception" - the company president still unaware of the distinction between embryo and fetus. The disclaimers warn anyone who's ever had an abortion, miscarriage, transfusion, or IVF, or is less than 8 weeks pregnant, that results may be "inconclusive". And instead of admitting to mistakes, the company oft evokes the "vanishing twin" excuse - that the detected gender was indeed present as part of a twosome, but died. It happens.

The current status of Acu-Gen and Baby Gender Mentor is somewhat unclear. The company president told NPR that the test was going on hiatus for a year while data accumulate. PregnancyStore.com, a marketer of Baby Gender Mentor, offers testimonial after testimonial, along with decidedly unscientific language in broken English, and at the end simply states, "Sorry. We are temporarily out of stock of the Baby Gender Mentor". Meanwhile, a class action lawsuit has been filed against Acu-Gen.

A Sea Change?

Baby Gender Mentor may, however, go down in history as contributing to the wake-up call to the agencies that should, and could, protect consumers against genetic tests being marketed when they are not quite ready for prime time. FDA hasn't regulated the test because it isn't a kit, and it doesn't address a disease or "condition" such as pregnancy. Nor is fetal (or embryonic) gender testing under the purvue of the Centers for Medicare and Medicaid Services (CMS), which enforce the Clinical Laboratory Improvement Amendments (CLIA), which currently ignore genetic tests as a specialty worth regulating. And the FTC has apparently not gone after the claims that are at odds with scientific evidence.

But change is in the air. The American Society of Human Genetics is currently drafting a position statement concerning DTC genetic tests. Rather than objecting to them across the board, the society will suggest that in some circumstances, they could be valuable, but that they all must be regulated and that they all must adhere to a policy of transparency.

Legislation is in the works too. Barack Obama (D-Ill) introduced a bill (the Genomics and Personalized Medicine Act of 2006) on August 3 that provides specific guidelines for the development and dissemination of genetic tests. The bill asks that CLIA embrace genetic testing, calls for guidelines for health professionals who may not be that familiar with genetics and genomics, and for Health and Human Services to develop risk-based protocols to review all tests.

Across the pond, the Special Non-invasive Advances in Fetal and Neonatal Evaluation (SAFE) network is a 19-nation effort to create partnerships that promote the development and use of routine non-invasive prenatal diagnostic and neonatal screening tests (http://www.safenoe.org/cocoon/safeorg/). The 5-year program began in March 2004, and includes among its objectives monitoring use of fetal DNA and RNA for detecting genetic disorders.

These new efforts focus on genetic testing for disease, but the experience with Baby Gender Mentor reveals what can go wrong when errors of intentional omission - that is, not including references to clinical trials of whether tests can work in a DTC format without causing harm - mislead consumers. For the downside of Baby Gender Mentor may be more serious than "gender disappointment." It may mean unnecessary invasive testing, mistaken termination of pregnancies predicted to be male in families with known X-linked conditions, and last but not least, the tainting of a technology that has been more than a decade in the making and will likely soon revolutionize prenatal testing - legitimately.

In the meantime, if anyone tries to sell you a cloned cat whose gender you can select, head the other way.

Ricki Lewis

Embryonic Stem Cells and Elections:
Sometimes You See It, Sometimes You Don't

This article by Susan Saulny in the New York Times over the weekend notes the limited visibility of embryonic stem cell research as a campaign issue in the Missouri Senate race, where incumbent Republican Jim Talent clearly opposes it and Democratic challenger Claire McCaskill clearly supports it. There’s a constitutional amendment on the November ballot which would unambiguously legalize such research in Missouri, but Saulny reports that neither candidate is highlighting their position on this issue in stump speeches or paid advertising. The reason, Saulny argues, is that the election is very close and both candidates need votes from outside their traditional party bases to win. McCaskill needs votes from rural southwestern Missouri (labeled as “Ashcroftland” by some observers), where voters are generally opposed to the stem cell amendment, and Talent needs votes from urban areas, which are more supportive. In this setting, neither candidate has any incentive to highlight their differences on this issue for fear of alienating voters whose support they need.

Saulny notes that embryonic stem cell research is a more visible issue in other races. In the Maryland Senate race where there is no incumbent, Democratic Representative Benjamin Cardin is highlighting differences in stem cell research policy with Lt Governor Michael Steele, who is the Republican candidate. Steele created a flap early in the campaign when he likened stem cell research to Nazi science experiments (he apologized profusely immediately afterwards) but is running hard to appeal to black voters, a traditional part of the Democratic base (Steele is black). As we’ve noted before, Governor Jim Doyle of Wisconsin is also pushing stem cell research as a major economic development effort in his re-election campaign.

Other races where stem cells have been more visible seem to be suburban seats that have traditionally been Republican, but are more moderate socially than the national Republican base. Republicans in these districts are frequently split between pro-business groups and social conservatives, and stem cells are a major dividing line in this split. In this sort of environment, playing up differences over issues like stem cells and even abortion may allow Democrats to appeal to independents and even moderate Republican voters. Two districts where this issue has surfaced recently are the 8th district in Illinois (northern Chicago suburbs) and the 25th in New York (which contains Syracuse and environs). In the Illinois 8th, incumbent Democrat Melissa Bean has started running ads highlighting the opposition of her opponent, Republican David Sweeney, to stem cell research. Bean knocked off a long-serving Republican incumbent to win election two years ago, and is receiving significant financial backing from the US Chamber of Commerce and other business groups. In the New York 25th, a Washington issues group called Majority Action is sponsoring a provocative television ad (which you can see in Art Caplan’s entry below) attacking Republican incumbent Jack Walsh’s position on stem cell research. Walsh has objected strenuously to the ad, claiming it misrepresents his position. Walsh, one of the more senior Republicans in the House, has historically been very popular in the district—he didn’t even have a Democratic opponent in 2004—but the race this time is more competitive.

The Missouri Senate race provides evidence for one traditional argument about the effects of party competition on candidate position—that it leads candidates in close elections to blur differences because they fear they may lose votes if they distinguish themselves from each other too sharply. The suburban House races provide evidence of the other view—that under the right political circumstances, competition will lead candidates to accentuate the differences between them. It’s worth noting that the candidates who are finding it in their electoral interest to emphasize the differences with their opponents around embryonic stem cell research are largely moderate, “pro-business” Democrats running in traditionally Republican areas.
Jim Fossett
AMBI Federalism and Bioethics Initiative

Still More Video, by Popular Demand

Bioethicist Jon Stewart takes you back to that moment, that magic moment, when Senator Brownback led the anti-stem cell lobby to new heights. It has to be difficult for Mr. Stewart when the Senators are actually more amusing than he. But he gets by. Don't email me for more video or this blog will become the theater of the absurd.

Quest for Cosmic Righteousness NASA's Chief Bioethicist, a Cheltenham Man, Tries to See that its Scientific Missions Do No Harm

That's their title. We're long overdue in noting this great profile of co-editor Paul Root Wolpe, president of the American Society for Bioethics and the Humanities and general go-to guy on ethics in space, psychiatry and sexual deviance (scholarship, of course). gHe is I am quite sure the only bioethics scholar who is working on, or ever will, the question of

...what should be done with an astronaut who "becomes psychotic and attacks" the other crew members to working with Williams in determining the level of radiation to which an astronaut can be safely exposed, he said.

Wolpe's NASA work is "frontier," said Art Caplan, director of the University of Pennsylvania's Center for Bioethics. "It opens doors merging engineering, ethics and medicine that you don't see anymore."

"How Come He Gets to Choose Who Lives and Dies?"

In some races around the country, Huffington Post notes, such as the Governor's race in Wisconsin, the Senate race in Missouri, and in the race in upstate New York where this ad is now running embryonic stem cell research is being used as a key differentiator between candidates. It will be very interesting to see if the huge number of disease advocacy organizations who supported embryonic stem cell research turn that support into votes next month!
Art Caplan

Senior Physicians in Israel Experimented on Elderly Patients

Israel News reports:

Four senior doctors at Kaplan Hospital in Rehovot and the Hartzfeld Geriatric Hospital in Gedera were arrested yesterday on suspicion of carrying out hundreds of illegal experiments on elderly patients without their consent.

The doctors - including Shmuel Levy, deputy director of Kaplan-Hartzfeld, who was responsible for Hartzfeld; Nadya Kagansky; and Alona Smirnov - are suspected of wrongful death through negligence, abuse of helpless victims, aggravated assault, fraud, violation of a statutory obligation and interference in an investigation.

The Tel Aviv Magistrate's Court yesterday extended the remand for Levy and Kagansky by three days and put Smirnov under house arrest for five days. A fourth suspect was released. Police searched the homes of all four suspects and confiscated documents.

Corresponding Editor Ricki Lewis
The Nutrigenetics War - Science vs Semantics

It sounds like a great idea. Extrapolate population-based gene/health biomarker links to the average consumer. Specifically, offer to match variants in DNA collected on a painless inside-the-cheek swab to “dietary and lifestyle” suggestions that just may include the purchase of personalized (and pricey) dietary supplements.

What’s the catch? After all, scientific support for gene-diet/lifestyle connections is robust. But what is curiously lacking, as far as I, the CDC, FTC, FDA, and who knows how many others can see, is investigation of the validity of applying pooled population health data to individuals. Consider an example: researchers genotyped 266 white women with breast cancer from western New York for the manganese superoxide dismutase gene, and compared them to age and neighborhood-matched healthy controls, also noting whether each woman ate a lot of fruits and vegetables or didn’t (1). For premenopausal women, having two copies of the “A” allele tracked with heightened breast cancer risk, but mostly only if they ate less than the median level of veggies. Does this mean that a black woman from Peoria with the same genotype should eat buckets of carrots to fight oxidation in her cells? That’s perhaps an exaggeration, but the gist of nutrigenetics.

Concerned that web-based marketing of such nutrigenetic tests to a less-than-science-savvy public is outpacing rigorous scrutiny of the premise, the Government Accountability Office (GAO) set up a sting operation. The results were reported at a hearing of the Senate Special Committee on Aging on July 27, and in a summary document [big PDF suitable for framing here].

The GAO Experiment

Here’s how the GAO targeted four nutrigenetics company websites. They took DNA from a 9-month-old girl and from a 48-year-old man. Then they concocted diet/lifestyle profiles for 14 “fictitious consumers,” 12 from the baby’s DNA, and 2 from the man’s. For example, the baby girl was transmogrified into a 6-foot-tall, 210-pound 45-year-old man who smokes and doesn’t exercise, drinks a lot of coffee, and eats a lot of fat. The baby also became a 72-year-old woman who weighs 100 pounds and stands 4’9”, regularly exercises, never smoked, doesn’t drink coffee, and eats fried foods. To make it interesting, the researchers also submitted cat and dog DNA but did not disclose whether the cat preferred Friskies to Fancy Feast or the dog Alpo to Purina so as not to tip their hand.

Results were not terribly surprising. Overall, the advice tended to track more with the made-up details involving exercise, smoking, and pigging out than to DNA variants, making one wonder why the tests are needed at all. But some results were disturbingly inconsistent. For example, the following fictitious consumers were all told that they were at increased risk of developing osteoporosis, high blood pressure, type 2 diabetes and heart disease: the male DNA/32-year-old male profile, the female DNA/33-year-old female profile, and female DNA masquerading as a 59-year-old male. The 59-year-old led a pretty healthy lifestyle, but the made-up 32-year-old man was a former smoker and the faux woman a smoker, neither of whom frequented the gym. All three were advised to purchase the same supplement package, tailored to their genes, to the tune of $1,200. The GAO subsequently found equivalents of these supplements at a regular store for about $35.

At least the fake trio who may face osteoporosis etc. were warned of familiar conditions. Another company used language so vague as to be meaningless. What do “faulty methylation patterns” mean to the average Joe or Jill? Is having methyls attached to your DNA a value judgment? What is “altered activity” in certain genes? “Brain aging”? Such pronouncements could be frightening or intimidating.

The GAO report is unfortunately a summary -- it is difficult to sort out which company actually did what, and my request for details has not yet been answered. Since multiple companies actually send the DNA to the same labs, assigning specific blame may be impossible anyway. But the overriding conclusion of the GAO report is clear: “Although these recommendations may be beneficial to consumers in that they constitute common sense health and dietary guidance, DNA analysis is not needed to generate this advice.” Case in point: suggesting that smokers stop smoking, and never-smokers never start. Ditto for “eat your vegetables” to up antioxidant intake, toxic spinach notwithstanding.

One Company’s Rebuttal

Not surprisingly, one of the skewered companies has written a very detailed and impressive rebuttal, taking on the GAO report point by point. This response starkly reveals the source of the controversy – and it is semantics, not science. (I won’t name the company because that isn’t really relevant. They have been helpful and forthcoming, and their website is a treasure trove of information, even if it doesn’t include any references that extrapolate the population studies to individuals. These might not exist.)

This nutrigenetics company’s website and others include disclaimers, such as “[This is] not a genetic test for disease or predisposition to disease, nor does it determine a medical condition,” followed by some variation of “if you’re sick, see a doctor”. Rather than diagnose, reads the rebuttal, the company “explains impacts on health parameters.” Like the confusingly positive labels on food supplements, nutrigenetics tests purport to assess such “parameters” as bone health, heart health, inflammation, antioxidant/detoxification, and insulin sensitivity.

Dubious Definitions

The disconnect between the GAO report and company websites stems from fuzzy interpretation of three definitions: a test can diagnose, predict (aka “detect predisposition”), or reveal elevated risk (aka “at-risk”). Some of the confusion stems from the fact that “at-risk” and “predictive” have very precise definitions in the human genetics field, with vaguer associations in plain English.

An analogy may clarify matters.

Imagine visiting a fortuneteller. If said seer diagnoses, she might say, “I see you are with a tall, dark, stranger.” Should she predict, she might say, “You will meet a tall, dark stranger.” But if her information is less precise, she’d say, “You are at increased risk of meeting a tall, dark, stranger.” This last option is what the companies claim they do; the GAO report claims it is the middle option. Figures in the government report, for example, use a label of “medical predictions” above lists of “increased risks”, as if the terms are synonymous. They’re not.

With this ambiguous language, what’s a health care consumer to do? Possibly panic. If a company reports that a cheek-swabber is at increased risk of developing, say, beriberi, might he or she interpret the suggestion as a diagnosis? One company’s language of “your genetic profile indicates you have variations in the B vitamin metabolizing genes … “ could be upsetting to someone not realizing that any copy of a gene is, technically, a variant. We all have them. (At least the websites use “variant’ and not “mutant”.) Yes, the websites provide excellent background material on genetics, with great references. But I doubt most consumers actually read all of it, let alone understand it.

The company rebuttal wisely steers clear of comparing their services to tests for well-studied single gene disorders -- such as for Huntington disease or BRCA breast cancer, -- likely because these tests underwent years of testing to see how people react to and use the resulting information. As far as I (and others) can tell, that simply isn’t known for nutrigenetics tests. Instead, the company uses as their model FDA’s quasi-guidelines for health claims on certain food products, which, like labeling on food supplements, steadfastly avoid mention of disease to the point of maddening obfuscation. The rebuttal offers an example from FDAspeak that must have won a contest for maximizing qualification: “While many factors affect heart disease, diets low in saturated fat and cholesterol may reduce the risk of this disease.” Similarly, a nutrigenetics company offers a “biological description of the effect of a genetic variation on cholesterol metabolism” – not a prediction that a person will meet a tall, dark stranger late at night in a garage and have a heart attack from fright.

Using the intentionally loose FDA food labeling guidelines as the model, I think, falls into the category of “two wrongs don’t make a right.” But it serves a purpose – it absolves the nutrigenetics companies, at least for now, from entering the fracas over genetic test regulation. That is an entire, huge area I’ll reserve for a future essay. In a nutshell, of the 900+ genetic tests, FDA regulates only about two dozen, as medical devices; the rest are dubbed “home brews”. The 1988 Clinical Laboratory Improvement Amendments of 1988 (CLIA) do not cover validity of genetic tests, despite many requests for their revision. Nor need labs publicly disclose the scientific basis for their tests, according to testimony of Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University.

If the rebuttal company wins the contest for delivering exactly what they promise, they lose ground when they attempt to justify the tests. They seemingly want to have it both ways, admitting that “… the presence of the particular variation does not necessarily mean that each individual will respond in the same way.” This is directly counter to their website’s “Why settle for a generic diet or lifestyle plan when you can have a personalized program based on your unique genetic make-up?” Homocysteine level is offered as an example. Ranges of levels of this amino acid track with genotype of the MTHFR gene, that’s true. But the rebuttal points out that high homocysteine is a risk factor, not a diagnosis, and can be measured without a genetic test. Again, why do the genetic test?

(Interestingly, this particular company’s website prominently sites their beginning as June 8, 2000, to coincide with the day that Francis Collins and J. Craig Venter announced the sequencing of the human genome. It’s common knowledge that the date was selected because it was the only opening on the White House calendar. The website claims that the company was founded on a “simple premise … to utilize the scientific information uncovered in this landmark study…” But many of the 19 genes that the company tests have been studied since as long ago as the early 1980s, when no one had even dreamed of a human genome project. An unfortunate bit of historical hype.)

First, Do No Harm

For most people, the advice offered by nutrigenetics companies probably can’t do much harm. But the company behind the rebuttal, at least, does not ask for information on health history or current drug usage. And so a problem could arise, given that we have no idea how most genes and environmental factors interact. The GAO report offers the example of a person with a retinoic-acid sensitive form of lung cancer being told to up his veggie intake. Extra beta-carotene could hasten the growth of the cancer.

I’m not too worried about the danger of web-based nutrigenetics tests, though, because consumers are savvy. I think the media reports on the Congressional hearing will go a long way to counter the positive spin that health and fitness magazines and the like have given these types of tests. Economics could be an issue. The genetic tests aren’t all that costly – 19 tests for about $250 isn’t unreasonable. Hopefully consumers, after they recover from the pricetag of the suggested supplements (assuming they do not have gene variants that compromise their heart health), will figure out cheaper ways to get what they think they need.

At least the dog and cat DNA samples were outed, returned because they “couldn’t be processed”.

The most recent addition to the team at The American journal of Bioethics, new Corresponding Editor Ricki Lewis is a regular contributor to many major science journals, author of several textbooks, and just generally insightful. Welcome.

Strategic Plan for California's World Domination in Stem Cell Research

The staff of the California Institute for Reproductive Medicine (CIRM), which is the agency managing the state’s stem cell initiative, has just released a draft strategic plan [download incredibly big PDF here] which outlines its goals and spending priorities for the next ten years. While there’s a lot here of interest to both scientists and bioethicists, on first reading two things stand out:

1—Lowering expectations—Like several other recent public commentaries by stem cell scientific types in the New York Times and the New England Journal of Medicine, the CIRM draft seems to downplay the possibility of major stem cell therapeutic breakthroughs over its ten year time horizon. The draft argues that it is unlikely that CIRM-funded research will be able to “fully develop stem cell therapies for routine clinical use” over this time period, but plans to advance therapies for several diseases to the stage of early clinical trials and have others in the pipeline. The plan’s goals call for “clinical proof” of restoring function in at least one disease, with therapies for 2-4 additional diseases in Phase I or II trials.

This assessment is less optimistic than some of the rhetoric heard during the recent debate in Washington over the bill which President Bush vetoed to expand the stem cell lines eligible for federal funding. It is also less sanguine than most of the disease advocacy groups that have historically been major supporters of embryonic stem cell research. Public comments by scientists have generally stressed the need for basic research funding, while advocacy groups have pushed for an emphasis on developing treatments. The plan envisions spending $800 million plus on both basic research and applied or “pre-clinical” research, and just over $650 million on clinical trials for new treatments.

2- “NIH free zones”—The draft also calls for spending some $250 million plus on new labs and other facilities that can operate without fear of violating current restrictions on funding ineligible stem cell lines with federal support. While perhaps wasteful and inefficient in the short run, such expenditures ultimately mean that California can formulate its own policies around what goes on in those labs without having to care very much about what the feds do or don’t do. It also means that other states contemplating stem cell research programs funded with their own money are likely to look to Sacramento, rather than Washington, for guidance on how to manage conflict of interest, egg procurement, royalty income distribution, intellectual property and the other complex ethical and legal issues that surround this research. While few other states can afford to spend this much money on new facilities, many appear to be spending smaller amounts of their own money or are relying on private giving or other sources to separate federally supported research from that supported by other financing sources. There may be a lot more of these states after elections in November—there’s a constitutional amendment on the ballot in Missouri, and several gubernatorial candidates of both parties have made support for stem cell research major elements of their platforms.

The development of funding streams independent of Washington and dedicated research infrastructure free of federal funding restrictions means that if federal policy makers do decide to do something definitive on stem cell research, it may not have much effect on anything. Having spent the money on new facilities and done the political heavy lifting to get ethical and commercial agreements in place, states, companies and universities may well decide that they like things the way they’ve got them and they don’t need to pay attention to the feds.

Jim Fossett, AMBI Federalism and Bioethics initiative

State Elections and Stem Cells

The latest issue of Stateline.org has an excellent round-up by Christine Vestal here on the state elections in which embryonic stem cell research has become a major issue. Two things are clear--- stem cell research is on the political agenda in a lot of states, and it’s not just an issue for blue state Democrats anymore.

As an election issue, stem cells are most visible in Missouri. There’s a constitutional amendment on the November ballot that would unambiguously legalize embryonic stem cell research, and stem cells have become a major issue in the U. S. Senate race between State Auditor Claire McCaskill (D) and incumbent Republican Jim Talent. While the Senate race is rated by political gurus as too close to call, the amendment is backed by a large coalition of faith, civic, patient and medical groups and commands a solid majority (60% plus) in recent polls.

Missouri’s hardly the only place stem cells are an issue, however. Incumbent Democratic governor Jim Doyle is running hard for re-election in Wisconsin on a platform that includes strong state support for stem cell research as a major economic development initiative. The state just announced a deal with the Wisconsin Alumni Research Foundation, which controls several key patents on stem cell techniques, which would give Wisconsin-based researchers and companies free access to the material and techniques covered by the patents, and Doyle wants to spend a lot of state money to attract companies to Wisconsin. Presumptive governor of New York Eliot Spitzer (he’s ahead by 50 points in the most recent polls) has put forward a proposal to spend $1 billion in state money to support stem cell research in that state, and Democratic candidate for Massachusetts governor Deval Patrick, who’s also well ahead in the polls, has also supported using state funds to support this research. Incumbent Democratic governor of Michigan Jennifer Grenholm is also running for re-election on a platform that favors eliminating the state’s current restrictions on stem cell research.

Republican candidates, some in so-called “red” states, are also supporting stem cells. Arnold Schwarzenegger in California, Robert Ehrlich in Maryland, Jodi Rell in Connecticut, and Kerry Healey in Massachusetts are all declared stem cell supporters, as are candidates of both parties in Kentucky. There are also initiatives under way in Georgia and Kentucky to get a Missouri-style constitutional amendment on the 2008 ballot.

Elections are very rarely about just one thing, and it would be a mistake to read any of these contests (except the Missouri constitutional amendment) as referenda on embryonic stem cell research. A couple of things are clear nonetheless. Unless the November elections also deliver veto-proof majorities in both houses of Congress for a revival of the stem cell bill President Bush vetoed last year, stem cell research policy in this country will continue to be set by the states, not the national government. If Doyle, Spitzer, and Patrick win their elections and are successful with their stem cell initiatives, for example, the amount of state money being spent on stem cell research is likely to expand significantly, and the rules governing that research will be the result of policies established in Madison, Albany, and Boston rather than in Washington. What does or doesn’t happen in Congress will be more or less irrelevant. Second, stem cell politics is slowly being detached from the abortion issue. Significant numbers of pro-life politicians and citizens support stem cell research, and some pro-choice groups, including womens health advocates, have proven to be less than enthusiastic about states supporting large scale stem cell research for a variety of reasons.
Jim Fossett

Amazon.com: Smart Mice, Not So Smart People: An Interesting and Amusing Guide to Bioethics: Books: Caplan Arthur L.

A certain frequent contributor to this blog has a notable new book of commentary on ethical issues in medicine, science and society that you can find in your bookstores or by clicking here.

The Plural of Anecdote is Not Ambien

In this month's issue of The Scientist I scream and yell about the ridiculous "studies" that purport to show that Ambien wakes up patients in persistent vegetative state or PVS:

... [Every nerd I know in bioethics has] had this experience: You bring work home and talk about concepts central to biomedical research such as evidence-based medicine, controlled trials, equipoise, peer-review, or impact factor. Friends' eyes roll up into their skulls in boredom. Yet the same topics come up in everyday conversation all the time, just framed in a different way: 'I know a person who lost his house to the cost of drugs,' and 'you know a guy who is alive because of Lipitor.' Heated arguments ensue about real problems in science, but driven by someone's single story.

Stories are not the enemy of good science and evidence-based medicine. Physicians make crucial but subtle changes in their practices based on individual experiences. Scientists all use intuition and inductive reasoning in the nascent period of an investigation. But anecdotes cannot substitute for either ethnography or controlled study. When Terri Schiavo became the world's test case for diagnosing persistent vegetative state (PVS), the emotional intonations about Ms. Schiavo waking up began to sound like Intelligent Design.

A paradox of biomedical research is that huge controlled trials, meta-analyses, and reviews of the literature are ubiquitous, but the number of 'case reports' - and journals comprised entirely of incidental 'findings' - is growing.

The media has no idea how to deal with case reports. The worst example of this in recent times was a case study of Zolpidem, the nonbenzodiazepine-branded 'Ambien' and approved by the US Food & Drug Administration for the treatment of insomnia. Physicians Ralf Clauss and Wally Nel have published, a few cases at a time, their very different use of the medication. The Guardian carried a breathless report of Clauss et al's August report in the journal NeuroRehabilitation of three cases involving patients who have been in PVS, they report, for more than three years. Claus and Nel grabbed the front page with the Guardian's report that they used Ambien to wake up these patients.

The 'investigators' had administered Zolpidem for between three and six years and saw each of the three 'treated' patients wake up each day as a result of the medication; one even 'caught a baseball.' When the medication wore off, the patients dropped back into PVS each evening.

Stunning science? It seemed so, too, back in 2000, when Claus and a different set of South African colleagues published in the South African Medical Journal on a single case with essentially the same outcome. In 2001 they made the same claim in a letter to the same journal. At no point did the investigators conduct an actual study of the phenomenon, with an IRB-approved research protocol or informed consent. Again and again they 'wrote up' their 'cases,' describing their work as innovative medical management rather than research. Journal editors, asleep at the switch, have been derelict in publishing bad research disguised as cases - in this instance a case with the impact of finding a life-extending potion or the presence of extraterrestrial life."

[click here to read the rest]

DDT, Malaria and Africa

This has been a heated controversy for some time, and it is not cooling down anytime soon. As many know, the use of DDT to control insects in agriculture has been highly restricted since the 1960's, due in no small part to Rachel Carson's Silent Spring, which connected DDT to cancer of the liver in humans and damage to bird reproduction. The successful restriction of DDT heralded the birth of the environmental movement in the United States as a political force, which means that any attempt to relax the restrictions is bound to spark a fierce ideological battle.

Now bring in Africa and the contemporary use of DDT in control of malaria. More than a million people die each year from malaria, mostly children under the age of 5, and 90% of the cases occur in sub-Saharan Africa. In the light of this public health catastrophe, observers over the years have argued that the benefits of using of DDT in small quantities for indoor spraying of walls and ceilings far outweigh the risks. Some have gone further, claiming that the restrictions on DDT have directly lead to millions of avoidable deaths, and thus crazy environmentalists (for some, read: eco-imperialists) have the blood of Africans on their hands. Worse still, the argument goes, while developed nations successfully eliminated malaria by using DDT in the 1940's and 1950's, those same nations now support a restriction on the use of DDT in poorer countries where where malaria is endemic, access to treatment is often limited, and economies are seriously impacted by the disease.

Two weeks ago, the World Health Organization officially announced its support of the use of DDT in indoor spraying, not only in epidemic areas (that was the old policy) but also 'in areas of constant and high malaria transmission, including throughout Africa.' The change in policy has strong backing from USAID and some US government officials, most notably Republican Senator Tom Coburn, who is quoted as saying:

“Finally, with WHO’s unambiguous leadership on the issue, we can put to rest the junk science and myths that have provided aid and comfort to the real enemy – mosquitoes – which threaten the lives of more than 300 million children each year.”

Republicans talking about health policy issues being resolved by a reference to scientific scholarship, of course, is heavy on irony, and naive to boot. The announcement by the WHO is hardly likely to put the DDT issue to rest in the short-term. While many (also in developing countries) have warmly welcomed the new policy, others remain flatly unconvinced. At the recent Intergovernmental Forum on Chemical Safety conference in Budapest, some delegates staged a protest over the new DDT policy, citing concerns about the potential effects of indoor spraying on reproductive health, neurological effects, effect on breast milk and increased risk of breast cancer, not to mention the possibility of resistance of mosquitoes to DDT. Inevitably, some raised the suspicion that dropping restrictions on DDT was ultimately driven by the financial interests of chemical industries in the US, rather than a concern for public health in Africa. A recent review article in the Lancet (2005) makes the usual song and dance, i.e. more research is needed:

Although DDT is generally not toxic to human beings and was banned mainly for ecological reasons, subsequent research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning, abrogating the benefit of reducing infant mortality from malaria. ... DDT might be useful in controlling malaria, but the evidence of its adverse effects on human health needs appropriate research on whether it achieves a favourable balance of risk versus benefit.

At the moment, how the risks relate to the benefits of using DDT in Africa still seem to be somewhat in the eye of the beholder. But given that the use of DDT in spraying is one of the few affordable and effective preventative interventions against malaria, and that hundreds of thousands die of the disease each year, the burden of proof would seem to fall on those who focus on the risks.
-Stuart Rennie

Two New Positions in Bioethics in Albany

UAlbany philosophy and AMBI hope to find two assistant professors to be appointed in the philosophy department and AMBI beginning in fall 2007, after hiring another in 2006. Three bioethics faculty added to a philosophy department in two years has to be a record. Of what kind I don't know. But a record. Clearly this city has too much bioethics. But apply anyway; Albany, at least according to Nature's article last week is a pretty cool place to do so.

The group of roughly 20 faculty who make up the Alden March Bioethics Institute, now just about a year old, include four who have joined our faculty in the past six months: Elisa Gordon PhD, MPH, Kristen Hessler, PhD, Summer Johnson ABD, and Sean Philpott PhD.

The new faculty, arriving in 2007, would be appointed to a philosophy department ranked 18th among U.S. doctoral programs in applied ethics by Brian Leiter's Philosophical Gourmet Report. These are ideal jobs for junior philosophers who want to spend time in a great philosophy department and in a rapidly growing, exciting bioethics program active in clinical ethics, research and publication, dissemination of scholarship (journals, book series) and teaching of undergraduates, medical students, and graduate programs (masters, PhD/MSBioethics [click here for more on the PhD program], MD/MSBioethics, JD/MSBioethics, MPH/MSBioethics, MSW/MSBioethics).

For more information see the philosophy department website, the Institute website, the advertisement for the position in detail, and contact the co-director of the dual-degree doctoral program Bonnie Steinbock at 518-442-4250.