Nominations Corner – Health And Human Services

The recent resignation of Secretary of Health and Human Services Kathleen Sebelius prompts a revisit of the slow march from nominee to confirmation.  While the President acted quickly to nominate Sylvia Burwell (current Director of the Office of Management and Budget) to replace Sebelius, the continuing paralysis of the Senate may mean it will be several months before she takes the job.

Normally the Secretary is, oddly enough, distanced from many of the science and technology functions the Department deals with.  But with the National Institutes of Health, Food and Drug Administration (FDA), Public Health Service (headed by the Surgeon General), the Presidential Commission for the Study of Biomedical Issues, and various research programs connected to Medicare and similar health programs, it would be tough for a Secretary to be completely detached from such actions.  In the case of Secretary Sebelius, perhaps her most controversial science and technology action is her decision to overrule the FDA in connection with the availability of emergency contraception.  While I doubt it will come up during the confirmation hearings, I think there will be an attempt to revisit the decision with a new person in charge of the Department.

(While we’re on the subject of Health and Human Services nominations, it’s worth noting that the latest attempt to nominate a Surgeon General has been blocked due – at least in part – on the refusal of some Senators to accept the nominee’s opinion that gun violence is a public health issue.)

Stanford Brings The METRICS To Research

John Ioannidis attracted some attention through a 2005 paper titled “Why Most Research Findings Are False.”  Ioannidis continued working in what is sadly just a niche – research quality assurance.  Part of Stanford’s School of Medicine, Ioannidis is now one of the directors of a new center, the Meta-Research Innovation Center at Stanford (METRICS).  This Economist article appears to serve as an early announcement about the center ahead of a formal launch in the coming days.  The center does have a website, but as of this posting, it’s not fully operational.

Ioannidis is joined as Director by Steven Goodman, Associate Dean of Clinical and Translational Research at Stanford.  His work has focused on proper inference, statistical analysis, and other components of effective research.  His interests include comparative effectiveness research and research outcomes.  The combination of experience between Goodman and Ioannidis seems tightly coupled to two major goals of the center -

“Our center aims to undertake rigorous evaluation of research practices and find ways to optimize the reproducibility and efficiency of scientific investigation. We aim to apply research methods to study how research is done, and how it can be done better.”

There’s an extensive laundry list of items METRICS wants to tackle.  Those interested in open research data (and methods), the various biases within research, conflicts of interest and commitment, and otherwise strengthening the reputation of the scientific enterprise should keep an eye on METRICS, and if they can, urge other researchers to take heed.  METRICS shouldn’t stand alone as a university research center focused on closing the gaps between research practices and research ideals.

About Those Three-Parent Headlines

A Food and Drug Administration advisory panel provided some filler for the 24-hour news channels this week.  The reason: discussion of mitochondrial replacement as a means of in-vitro fertilization (IVF).  It involves a ‘donor’ cell which has its nucleus removed to receive the nucleus of the mother (it bears some resemblance to somatic-cell nuclear transfer, except there is an additional DNA source involved).  This method could be used for situations where the mother has mitochondrial defects that could be passed on to the offspring.

The method gets the superficial cable news attention because the resulting offspring would have DNA from all three donors.  While the Presidential Commission for the study of Bioethical Issues has not weighed in (it doesn’t meet again until June), the FDA panel discussed the state of science and research on the technique, as well as the design requirements for early-phase clinical trials.  Researchers have produced monkeys via this IVF technique, but panel members were reluctant to recommend human trials at this time.

Over on the other side of the Atlantic, the U.K. is further along in regulating the technique.  The appropriate advisory bodies started assessing mitochondrial replacement in 2011, and the government announced last year that it was working on regulations.  It issued a consultation on Thursday for the draft regulations (questions of interest are on pages 27-28).  Responses will be accepted until May 21.

Should Science Have Run The Keystone Editorial?

In the latest (February 21) edition of Science, editor-in-chief Marcia McNutt, former head of the U.S. Geological Survey under President Obama, has an editorial (free, with registration) on the Keystone XL pipeline, a project that the U.S. government has not yet decided to pursue (or not).  McNutt, in a reversal of her previous position, believes it should be approved.  Her rationale hinges on the capability of the U.S. government to extract concessions from the pipeline owners and manufacturers to ensure better environmental safety than transporting the oil via rail and truck.

McNutt is more than entitled to her opinion on the matter, as well as her own criteria for choosing the way that she has.  But I’m not sure this had any business being aired in the pages of Science.

My recollection of Science editorials is hardly comprehensive (especially since I am not a subscriber).  But I find it difficult to see why the pipeline extension is worthy editorial fodder for Science, certainly with how this editorial is written.

Science editorials have certainly been political, and have certainly made policy recommendations in the past.  I’ve even supported a scientific journal making a recommendation for political office – provided it was open and transparent about what it was doing.

But in all of these matters (again, based on the editorials I have read), there was some connection to the specific interests of the journal, its publishers, its readers, or the relevant scientific communities.

I don’t see any such connection in this editorial.

McNutt’s editorial is written from her individual perspective (the number of times I is used in the piece stood out for me).  Nothing in the editorial reflects her position as editor-in-chief nor concerns specific to the journal or its publisher, AAAS.  Her reasons for supporting the extension are conditioned on successfully obtaining concessions from the pipeline owners and manufacturers – a policy process that may have very little to do with relevant science.

Certainly an editor is expected to have some influence on the perspective of the publication she edits.  But that perspective should be connected to the mission of the journal or the interests of its readers.  Many readers of Science may agree with McNutt.  But I doubt that has anything to do with their membership in AAAS or interests in science and technology.

Whether Stem Cells Can Be Patentable May Be The Least Of Commercial Challenges

Two recent actions involving the Food and Drug Administration (FDA) suggest to me that the matter of whether stem cell patents are valid may not be so critical.

The D.C. Circuit Court of Appeals ruled last week that the FDA has jurisdiction over stem cells cultured for therapeutic use (H/T The Scientist).  This decision upheld a lower court ruling that considered the act of culturing the cells more than ‘minimal manipulation,’ and therefore subject to FDA drug oversight regulations.

(IANAL, but I think this decision could be used to strengthen the case that stem cell patents – at least for cultures of said cells – would be valid.  After all, if there was more than minimal manipulation, wouldn’t that be sufficiently transformative to make the cultures no longer products of nature?  Again – I Am Not A Lawyer.)

Aside from the legal matters, there appears to be a big regulatory mismatch that will hinder commercialization of stem cell treatments.  In the February 6 edition of Cell Stem Cell researchers note (H/T The Scientist) that differing regulations between the National Institutes of Health (NIH) and the FDA may reduce the number of stem cell lines that could be used in clinical practice.

FDA regulations require that stem cell donors be screened for various diseases (so that treatments derived from those cells cannot infect others).  NIH regulations – not focused on commercial applications of stem cell research – do not have this requirement.  Now it is possible, as the article from The Scientist notes, for the FDA to allow some treatments to be approved without such a screening, but some alternative measure will likely be needed to mitigate the risk of infection.

Bioethics Commission Seeks Public Input On Neuroscience Applications

As part of its work on the ethics of neuroscience, the Presidential Commission for the Study of Bioethical Issues is seeking public input.  Per this notice from the January 31 edition of the Federal Register, the commission “seeks public comment on the ethical considerations of neuroscience research and the application of neuroscience research findings.”  Comments are due by April 1.

The request certainly is intended to support the Commission’s work on the ethics of neuroscience research and the applications of that research.  Of particular interest to the Commission are the following topics:

  • The diversity and scope of ethical considerations related to neuroscience as a field;
  • core ethical standards that guide neuroscience research, including consistency (or lack thereof) across disciplines, and potential tension among the guiding standards;
  • advances in neuroscience research that raise novel ethical issues or heighten existing ethical tensions;
  • whether emphasis on particular aspects of the Common Rule (or other research ethics regulations) is needed given the particular implications of some neuroscience research or whether any part of the Common Rule needs clarification in order to adequately protect participants in neuroscience research specifically;
  • potential implications of discoveries that might flow from studies of the brain and questions that might arise from neuroscience research findings and their applications, including questions about the potential implications for privacy, personal agency, and moral responsibility for one’s actions; stigmatization and discrimination; and the appropriate use of neuroscience in the justice system;
  • strategies for integrating from a project’s inception ethical considerations into neuroscience research, technological development, and scientific research generally; and, ethical considerations concerning communication about neuroscience research and neuroscience research applications by scientists, journalists, and others.

The Commission is meeting in Washington on February 10 and 11, and this request will certainly be mentioned, if not discussed in detail.  Of particular interest may be how this project will tie into the BRAIN initiative that prompted the Commission’s interest in the subject.

In New Report Bioethics Commission Recommends Expecting Incidental Findings

Today the Presidential Commission for the Study of Bioethical Issues released its report on incidental findings.  This project started at the beginning of the year, and focuses on findings that were beyond the aims or scope of a particular test or procedure.  The ethical consequences of such findings can be most keenly felt when they involves human subjects and/or medical patients (see this article on The Atlantic’s website for a specific medical case).  Such findings may not be information that a subject/patient is seeking, which adds an additional wrinkle to determining how to best approach the person and respect their rights to choose and one’s obligations to provide appropriate and effective treatment.

But they can be found in many different places, which is why the report, called Anticipate and Communicate, has a subtitle of Ethical Management of Incidental Findings in the Clinical, Research and Direct-to-Consumer Contexts.  It’s also why this isn’t the first Commission report to address incidental findings.  It was mentioned in the Commission report on genome sequencing (and probably not heeded by anyone at 23andMe, based on FDA action taken against that company)

Not that brief blog posts are the most reliable source of deep insight, but in an instance of covering a report that deals a lot in context, I have to emphasize that you really should read the report and not simply this post.  As the report notes (Executive Summary, page 2):

“Discovering an incidental finding can be lifesaving, but it also can lead to uncertainty and distress without any corresponding improvement in health or wellbeing. For incidental findings of unknown significance, conducting additional follow-up tests or procedures can be risky and costly.4 Moreover, there is tremendous variation among potential recipients about whether, when, and how they would choose to have incidental findings disclosed. Information that one recipient regards as an unnecessary cause of anxiety could lead another recipient to feel empowered in making health- related decisions.”

The tl;dr – I’m not comfortable just summarizing the report findings and leaving it at that.  it’s a complex issue that cannot easily be generalized.  The Commission takes a general approach in its report, outlining how an ethical analysis of incidental findings can be conducted, and encouraging those with expertise in the technology and scientific knowledge related to a particular context to do what they can to anticipate possible incidental findings (not all of them can) and communicate those possibilities to the people being tested, as well as the public that may be tested at some point in the future (or have something revealed about them through the testing of others).

Charles Monnett Settles Whistleblower Case; Should Interior Revise Scientific Integrity Policy?

Charles Monnett, who was temporarily suspended in 2011 after accusations of scientific misconduct, recently settled a whistleblower complaint with the Department of the Interior (H/T Roger Pielke, Jr.).  Monnett has officially retired from the Department received a cash settlement, and had a letter of reprimand removed from his file (placed there for supposedly leaking agency documents).  The Department does not acknowledge any liability in the matter, and states that the agreement was entered into on their part to avoid the costs of litigation (which may well have influenced Monnett’s decision to accept).

As background and refresher, Monnett worked for the Deparment’s Bureau of Ocean Energy Management.  In 2010 a scientific integrity complaint was lodged against him, but the department did not find evidence to suggest scientific misconduct, but reprimanded him for leaking internal government documents.  Monnett alleged actions by the Bureau and the Department’s Office of Inspector General constituted misconduct and harmed the integrity of his scientific efforts.  The department found (cases 290 and 295) that the actions of both parties were consistent with the nature of such investigations and did not violate the scientific integrity policy.

Arguably the first test case for scientific integrity policies following the big push from the Office of Science and Technology Policy, Monnett’s case involved both the scientific integrity policy (which he was accused of violating) and general policies and laws concerning whistleblowing activity (which is mentioned in the scientific integrity policy).  While there would appear to be resolution in terms of a partial restoration of Monnett’s status and name following charges that could not be substantiated, I think there’s a reasonable set of questions to ask about what such restoration means in the context of scientific misconduct.

Could scientific integrity policies benefit from stronger language concerning whistleblowing and retaliation?  Ultimately these policies will rise and fall based on the people, processes and culture in place to implement them, but the language provides a starting point.  Do accusations of scientific misconduct (which are not all the possible violations of scientific integrity policies) warrant the additional scrutiny and protection intended for those trying to reveal other kinds of inappropriate conduct?

I think it’s worth considering how the additional consequences to the accused of claiming scientific misconduct can be handled in a way that’s as fair as possible to all concerned.  But since the Office of Science and Technology Policy seems to think they’ve done all they need to do in this area, the consideration will have to come from other interested and/or aggrieved parties.  Any takers?

New Survey Provides Snapshot On DIY Biology

The Woodrow Wilson International Center for Scholars recently conducted a survey as part of a report on the growing do-it-yourself (DIY) Biology movement.  The newly released report (H/T ScienceInsider) from the Synthetic Biology Project is apparently the first of its kind to track what activities the community is involved with.

The report authors are interested in countering existing stories about the DIYBio community that don’t match with what their research (and survey data) have demonstrated.  The brief takeaway, from their perspective – the threat posed by this research (and these researchers) has been overstated in the press.

While the authors are careful to note that their work is a current snapshot of the field, I am concerned that the press connected to this report may oversimplify what’s going on.  In other words, the new stories will be about how the old stories oversold the magnitude of what is going on in the field and the possible threats of what could be taking place.

I think the most productive recommendations from the report will be those focused on how to grow, support and manage research in this area moving forward.  As a DIY community is not necessarily connected to existing institutions, having the capacity to educate interested researchers and provide them spaces to work is not guaranteed.  Such resources could also ease the burden of monitoring and guiding the research moving forward.  A previous report from the Synthetic Biology Project suggests to me that at least some community self-regulation would be useful in the future, as federal action is coming slowly.

Either way, this survey needs to be the first of several, and not the end of a discussion.

Florida Continues To Use New Drug For Executions

On Tuesday Florida executed its second condemned man with the use of midazolam in its three-drug protocol.  The drug is still the subject of a lawsuit by death row inmates because of concerns midazolam (intended as an anesthetic) may leave prisoners in extreme pain as their lives are ended.  The reasoning is that such pain would violate the Eighth Amendment prohibition against cruel and unusual punishment.

Florida has turned to midazolam because of restrictions on other drugs have limited supplies.  Ohio was scheduled to use midazolam for the first time in an execution on the 14th, but the inmate requested that his organs be donated.  This prompted the governor to stay the execution pending an examination of how inmates could donate their organs post-execution.

But, as might be expected, Texas continues to execute with only small adjustments.  They are not using midazolam, but their reliance on compounding pharmacies and heightened secrecy surrounding how its drugs are acquired have prompted a lawsuit.  Missouri, which had delayed an execution due to concerns over how it obtained propofol, will move forward with that execution later this month.  It will use pentobarbital, but there are similar concerns over how it obtains its drugs.

If there is to be action from these court cases around compounding pharmacies, it will be over possible violations of existing state laws around public information and/or state procurement of resources.  Courts have not been sympathetic to concerns over how effectively drugs have been tested.  There will be more opportunities to check this hypothesis as states continue to execute prisoners.