Earlier today, the March of Dimes issued a comprehensive report on birth defects. The report, written by Arnold Christianson, Christopher Howson, and Bernadette Modell, estimates that every year an estimated 7.9 million children (6% of total births worldwide) are born with a serious birth defect of genetic or partially genetic origin (see here for the press release, here for the executive summary, and here for the full report). The report provides a thorough and useful overview of the problem and is important reading.

At least 3.3 million children under the age of five die from birth defects each year, and an estimated 3.2 million may be disabled for life. Birth prevalence from country to country ranges from a high of 82 per 1,000 to a low of 39.7 per 1,000 live births worldwide. More than 90 percent of all infants with a serious birth defect are born in middle- and low-income countries. But the main impetus for the report stems from this fact:

Up to 70% of the birth defects that occur could either be prevented or the children affected offered care that would be lifesaving or significantly reduce disability.

The report ranges from the five most common serious birth defects of genetic or partially genetic origin (congenital heart defects, neural tube defects, the hemoglobin disorders, Down syndrome, and glucose-6-phosphate dehydrogenase deficiency), to common recessive disorders (cystic fibrosis, oculocutaneous albinism), to congenital infections (toxoplasmosis, syphilis, varicella-zoster, rubella, cytomegalovirus, herpes simplex virus), to birth defects arising from maternal malnutrition or exposure to teratogens (spina bifida, congenital hypothyroidism, fetal alcohol syndrome), to factors influencing the global distribution of birth defects (malaria, consanguineous marriage, parental age, migration, poverty).

The authors note several misperceptions that in their view have made birth defects a relatively low priority for donors and health care agencies. First, health policy makers have not been aware of the extent of death and disability attributable to birth defects. Second, there has been the belief that effective care and high-tech interventions are beyond the means of low- and middle-income countries (on this score they cite heartening advances in preventing and treating sickle cell anemia in Nigeria, thalassemia in Iran, and neural tube defects in China). Finally, they cite the belief that attention to birth defects will draw funding away from other high priority maternal and child health efforts. On this last point, they note the obvious cost effectiveness of relatively straightforward measures like folic acid fortification of food to prevent neural tube defects, which not only prevents 500-550 cases per year in the US, but is estimated to save approximately $400 million annually as well.

Recommendations? Here’s a partial list:

Educate the community.

Promote family planning.

Ensure a healthy, balanced diet during a woman’s reproductive years.

Control infections in women of reproductive age.

Optimize maternal health.

Train physicians and nurses in recognizing birth defects and in the essentials of medical genetics.

Establish child health services to care for infants with birth defects.

Establish national capacity for surveillance and monitoring.

Promote lay support organizations.

Establish peri-conception medical services.

Implement pre-conception or prenatal medical genetic screening to identify couples at risk.

Establish newborn screening for metabolic disorders.

An ambitious agenda, no doubt, but the examples of success that the authors cite suggest that many of these goals are achievable.

One particularly interesting topic, in my view, is that of consanguineous marriage. The authors note that it’s accepted by a minimum of 20 percent of the world’s population, largely in the Eastern Mediterranean, North Africa, and South India. As a result, they report this striking estimate: at least 8.4 percent of the world’s children have related parents. Given that the risk for serious disability and/or neonatal and childhood death is almost doubled for the offspring of first cousins, this is a major factor in the incidence of birth defects (this is demonstrated clearly in the report’s Figure 5, comparing the incidence of birth defects in British Pakistanis with Britons of North European descent). It isn’t clear from the report that the authors view a reduction in consanguineous marriage as a realistic part of the overall strategy to combat birth defects, but given its impact, it’s hard to see how it can be avoided.

Read the whole thing.

Smith et al.

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

Zhu et al.

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus

Yoshiura et al.

A SNP in the ABCC11 gene is the determinant of human earwax type

Shiba et al.

Dominance relationships between self-incompatibility alleles controlled by DNA methylation

Comments welcome.

Ikeda et al.

Spectrin mutations cause spinocerebellar ataxia type 5

Dunoyer et al.

Induction, suppression and requirement of RNA silencing pathways in virulent Agrobacterium tumefaciens infections

Jordanova et al.

Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy

Bonnen et al.

Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia

Boyden & Dietrich

Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin

Weiss et al.

The sex-specific genetic architecture of quantitative traits in humans

Comments welcome.

If you like interviews—and I usually can’t get enough of them—you can only applaud the launch of the interview series in PLoS Genetics, off to a good start with one-on-ones with Nicholas Wade and Tom Cech. The chat between PLoS interviewer Jane Gitschier and Wade is a wide-ranging one with a journalist who has worked for Nature, Science, and The New York Times (as an editorial writer and a news writer). I imagine there aren’t many people who can make that claim. Tom Cech’s personal and scientific history is of course interesting as well, and I took note of this comment in particular, at the tail end of a discussion of changes in RNA science:

But look back at Jacob and Monod’s early thinking that the lac repressor might be an RNA molecule. Once the lac repressor was proven to be a protein, people got all focused on gene expression being regulated by proteins. But if they had been looking in bacillus, rather than in E. coli, they would have found riboswitches built into transcripts that bind small-molecule metabolites and control transcriptional termination or translation. So the old Jacob/Monod model was actually right, but for a different branch of bacteria.

I had heard precisely the same observation when visiting the labs of Ron Breaker and Saeed Tavazoie, as part of a discussion I’m sure many people are having as to how regulatory RNAs could remain a secret for so long. Sydney Brenner has made an analogous point when he refers to ‘Morgan’s deviation’—Thomas Hunt Morgan’s fateful decision to turn from embryology to genetics, and all of the scientists he took with him. The dominance of the protein-regulatory paradigm as the consequence of a choice made by two scientists some 50 years ago is no doubt an oversimplification, but these kinds of counterfactuals are interesting and fun to think about. The conversation is currently on low simmer (see here and here), but perhaps we’ll hear more about it this in June at the Cold Spring Harbor symposium on regulatory RNAs.

Seed magazine has recently launched a site called ScienceBlogs, which brings together a number of good blogs, including several we read frequently and link to on this page (Pharyngula, Gene Expression, The Intersection, Evolgen). As a result, the URLs of these blogs have changed, and we’ll be updating these shortly. The new site abandons some of the idiosyncracies that characterized the design of the individual pages (for better or worse), and provides a one-stop shop for those who like a daily dose of science blogging.

Kyttala et al.

MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome

Peisajovich et al.

Evolution of new protein topologies through multistep gene rearrangements

Grant et al.

Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes

Malek et al.

Physiogenomic resources for rat models of heart, lung and blood disorders

Skol et al.

Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies

Smith et al.

The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

Comments welcome.

Obviously it will take some time for the dust to settle from the stem cell fraud case. It’s certainly disheartening to see that such an apparently promising result was faked, and no doubt this plays into the hands of those who find the entire endeavor disreputable. But the work will go on, and I completely agree with the bloggers at the American Journal of Bioethics (who have been all over this story) that the question of whether the US federal government will fund this work becomes less and less relevant. The states are the big players, and the Hwang fiasco may actually jumpstart some new work now that the key task of generating individualized embryonic stem cell lines has been put back on the table.

That said, I don’t have anything else to add to the avalanche of commentary that is already out there. I would like to say something about peer review, however, which takes a beating whenever a bad apple turns up in the published literature. Everyone likes Winston Churchill’s line about democracy: it’s the worst form of government except all those other forms that have been tried from time to time. The same goes for peer review, they say (see here). This is appealingly modest, and properly recognizes that all human institutions will be imperfect because all human beings are imperfect.

But this strikes me as damning something with faint praise. So let me go out on a limb and say something heretical: peer review really works quite well.

Really.

Phil Campbell, editor of Nature, makes a strong case, but here are some additional thoughts.

From the questions I sometimes get, one might think that the peer review system is riddled by unacknowledged conflicts of interest, and inadequate or incompetent reviewing. Add in a general tendency to give sexy results a free pass or, depending on whom you’re talking to, to disregard truly important findings out of a lack of imagination, and it’s not a pretty picture. Do such things ever happen? Sure (see above re: human imperfection). But I’ve been an editor at Nature Genetics for more than five years now, and if I had to offer one overriding impression of peer review it would be the conscientiousness of the vast majority of reviewers and editors that I’ve worked with (this may seem self-serving, but there you go). Our reviewers are among the busiest people you’ll ever meet, and yet they labor over the details of manuscripts, considering them in the context of the prior literature, and offer thorough advice on how to improve them, even if they don’t think a particular paper is a good fit for the journal to which it’s been submitted. On occasion, they suggest that a result is flat-out incorrect. Their advice is often lengthy and remarkably thoughtful. As a result, the scientific literature as a whole is significantly better than it might otherwise be: important controls are added, stories are made more complete, new and interesting experiments are carried out, discussions are made clearer, methods are fleshed out. I know that at least one of these things is true of most papers that go through the process.

Perhaps you have to wade through hundreds or thousands of reviews to get a sense of this. Planes that take off and land safely don’t make the headlines.

I’m sure there are a lot of opinions about this. The floor is yours.

This is a bit behind the curve, but I can’t help commenting on an interesting confrontation my Nature News colleague Jim Giles seems to have had at last year’s meeting of the Society for Neuroscience (see Day 2: Rejected by Science). Here’s the best part:

This afternoon I wandered down to a session on how to get published in Science. As I mentioned yesterday, this went head-to-head with an equivalent session run by Nature and I wanted, out of curiosity and a healthy dose of journal rivalry, to see which would attract the most researchers.

I checked numbers first at Nature—around 170 people—and strolled down the corridor to Science. They had the edge, I thought, since they were serving post-session drinks. I had just started my head count when up strolled a rather formidable looking lady with a Science badge on.

Her: You’re from the competition. I think you should leave.

Me: Erm…really?

Her: Yes. It’s not fair that a Nature editor attends this talk.

Me: But I’m not an editor, I’m a journalist.

Her: A journalist? So you want to get published in Science?

Me: Erm…no…actually I’m just curious.

Her: Well I think you should leave.

Nothing like a little intrigue at the SfN, huh? Well, if you’re wondering why it should be easier to get into one of George Bush’s press conferences than to attend a public talk by an editor for a science journal, the answer is: it shouldn’t. Most professional editors at journals like Nature, Science, Cell etc. give talks on editorial policy and how best to navigate the peer review process. While it’s conceivable that such a talk would indicate an editorial interest in particular subject matter that would be surprising, it’s not likely, and the easiest way to get published in such a journal is rather obvious, as pointed out by my colleague Annette Markus.

These talks are generally useful in dispelling some of the mystery surrounding what editors do. Who reads the submissions? How do you decide which manuscripts are sent out for formal review? How do you choose referees? What’s the best way to revise a paper when some of the referees’ comments seem off base?

We’ll be addressing some of these questions at Free Association in coming weeks, but if an editor comes to town to give a talk in the meantime, by all means stop by. I’m sure you’ll find it interesting, even if the formula for the world’s most famous soft drink remains a secret.

Kuroki et al.

Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway

Comments welcome.

Happy New Year.