Maternal versus paternal effects on autism

All opinions my own and do not necessarily reflect those of Novo Nordisk

A report just out in JAMA Pediatrics (behind a paywall, but you can see the abstract at the link) reports the intriguing finding (by the way, just for the record, in blogging I’m finding it hard to find synonyms for “interesting.”  Please bear with me) that the recurrence risk for siblings of children with autism is seen even with half-siblings, albeit at a lower rate.  And more intriguing, the risk for sequential half-siblings is higher when the siblings share a mother than when they share a father.

This strikes a chord to me because it is consistent with other recent research I’ve described before, in which the presence of maternal autoantibodies to certain sets of neural proteins was predictive for development of autism.  As the abstract for the current work says, “the significant recurrence risk in maternal half-siblings may support the role of factors associated with pregnancy and the maternal intrauterine environment in ASDs.”  Whether maternal autoantibodies are associated with recurrence risk in this cohort is unknown.  The earlier study was at UC Davis; this one is from Denmark.  I’m generally of the mind that autism is an extremely complex collection of related syndromes, with many different contributing factors (but not vaccines!), so I think it’s best to just do the experiment and test for autoantibodies in the mothers of recurrent siblings.

And the nice thing about a country like Denmark is that this is probably feasible.  Unlike some other nations with extremely fragmented and incomplete health care systems (*cough*United States*cough*), Denmark has very good, integrated medical records.  Denmark also has very high standards for ethics and consent.  So finding a reasonable cohort of mothers and recontacting them may allow a test of whether an association to autoantibodies can be found here as well.  All towards figuring things out, all good.

I wrote to the authors of the study to ask about their work and how it might relate to the autoantibody studies and received the following email response from Dr. Diana E. Schendel of the CDC, via Therese Grønborg:

“Since our paper supports a role for maternal intrauterine effects in ASD, in addition to familial factors, our results are consistent with findings such as the (sic) UC Davis of maternal-derived factors that put the fetus at risk for ASD in pregnancy. One of the pregnancy related factors investigated in ASD etiology concerns abnormal immune system function – perhaps in the mother or perhaps in the fetus – that could impact brain development.

It is important to note that ASD has many potential causes and our study supports the notion of many etiologic pathways – both through family history and prenatal fetal  environments.”

This is a great statement as it jibes with my own views on diseases like autism–that we’re still very early in our understanding of what creates the presentation of a complex phenotype like autistic behavior, and that we need to keep looking and certainly not expecting simple explanations.  Finding explanations is not going to lead directly to new drugs, but greater understanding and a more personalized and nuanced view of each child’s challenges will help maximize their chances of finding success in life.

Do Biopharma workers hate their jobs? Answer, I don’t think so, but…

All opinions are my own and do not necessarily reflect those of Novo Nordisk

A colleague of mine when I worked for Merck used to drop by my office to discuss project management, and one of his favorite terms was “engagement.”  I was reminded of this when the people at Gallup published their most recent results about their polling of the American workplace.  You can find their report here, and a writeup here.  One of the interesting/sad findings was that only 30% of their survey respondents (and there were 25 million respondents) report being engaged in their work.  This astounds me.

One of the many perks of science is that far more than 30% of the people I work with on a daily basis are very engaged in what they do.  By engaged, let me refer to the Gallup report:  “Gallup defines “engaged” employees as those who are involved in, enthusiastic about, and committed to their work and contribute to their organization in a positive manner.”  Sounds like a good working definition.  There are a number of reasons to go into science, but rarely do I find people saying they’re doing it for the money.   Probably because that just doesn’t compute when you say it out loud. Continue reading

Lack of replication no surprise when we’re studying really complex problems

All opinions are my own and do not necessarily reflect those of Novo Nordisk

For another nice take on this topic see Paul Knoepfler’s blog post here.

One of the sacred (can I say sacred in reference to something scientific?) tenets of the scientific method is reproducibility.  If something is real and measurable, if it’s a fact of the material world, then the expectation is that the result should be reproducible by another experimenter using the same methods as described in the original report.  One of the most well known (among physicists anyway) examples of irreproducible data is the Valentine’s Day Magnetic Monopole detected by Blas Cabrera back in 1982.  Great experimental data.  Never repeated, and therefore viewed as insufficient proof for the existence of a magnetic monopole.

So it’s troubling that in the past few years there have been numerous stories about the lack of reproducibility for different scientific experiments.  In biomedical science the number of  reports on the difficulty of reproducing results has gotten so great that the NIH has begun thinking about how to confirm and require reproducibility of some kinds of experimental results.  Just a few days ago another field, that of psychological priming, saw the publication of an article that the effects of “high-performance priming,” could not be reproduced.  This is another field undergoing serious questioning about whether/why results don’t reproduce, with commentary from such luminaries as Daniel Kahneman. Continue reading

Are market cap and present cash flows the best way to measure innovation?

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Forbes, with the help of the folks from The Innovator’s DNA recently published their coverage and rankings of the 100 most innovative companies.  I’m particularly interested in their ranking method, as it contains elements that are near and dear to my heart–namely, metrics and crowdsourcing.  In a nutshell, they describe how they use a company’s current market capitalization, along with it’s current net present value based on cashflows, to extrapolate how much the market feels the company has in potential.  The method nicely incorporates crowdsourcing in that the market cap measures how much investors as a whole think a company is really worth, now and in the future, and if that’s higher than expected based on cashflow, that suggests investors are factoring in a bonus to value based on future expectations.  Higher future expectations are interpreted as investors seeing a particular company as innovative and having the potential for great leaps forward in offerings and/or income.

I really like using the crowd in this way, and would love to see an analysis that retrospectively looks at these kinds of values over, say, 1970-1990, and combines that with a mature assessment of which companies have been adjudged by business historians to truly have been innovative standouts, which is not the same as business successes.  We say now that Bell Labs was one of the most innovative places on the planet in the 1900s.  Would the same have been said at the time?

At the same time, I can’t help musing if this process couldn’t be made even better.  Recognizing innovation when it’s happening has obvious advantages for anyone looking to get into the next amazing thing, whether as a participant, an investor, or a policy maker.  So let’s start by examining where there might be shortfalls to the Innovator’s DNA method. Continue reading

What does the Hela genome agreement imply for consent and genome data usage?

All opinions my own and do not necessarily reflect those of Novo Nordisk.

A fair amount of reporting (for example here, here and here) has gone into the recent news that the NIH and the descendants of Henrietta Lacks have reached an agreement about the conditions under which the genome sequence of the HeLa cell line will be shared.  The basic parameters are that researchers wanting access to the data will need to apply for permission, the application committee will include members of the Lacks family, any publications will acknowledge the contribution of the Henrietta Lacks, and future genome sequences will be submitted to dbGAP.

This is a generally welcome development, and in no small part due to the work of Rebecca Skloot.  Her book, The Immortal Life of Henrietta Lacks provided the impetus to the current developments by popularizing the story of Ms. Lacks and the cell line derived from her tissues.  However, this agreement also can be seen as a precedent of sorts, and the future implications for the ethics of consent, genetic information sharing and genomic research are unclear.

Whose genome is it, anyway?

In Pasco Phronesis, David Bruggeman penned a post on some of the possible implications.  He discusses one of the key elements of genetic consent that I generally haven’t seen elaborated on much in the current literature: familial consent and exposure.   To what extent do those who share part of a sequenced genome have a say in the granting and rescinding of consent for the usage of genetic information?   Continue reading