Gene Therapy May Have Revised Oversight

The National Institutes of Health (NIH) will stop requiring special review of gene therapy trials (H/T ScienceInsider) currently conducted by the Recombinant DNA Advisory Committee (RAC).  NIH Director Francis Collins justified the decision, which is based on recommendations from a study it requested of the Institute of Medicine, by noting the progress in the field since the formation of the RAC over 40 years ago, as well as the additional regulatory reviews in place for this kind of research.  The RAC would remain to review special kinds of gene therapy trials, provided they meet the following requirements:

  1. The protocol review could not be adequately performed by other regulatory and oversight processes (for example, the institutional review boards, institutional biosafety committees, and the FDA).
  2. One or more of the following criteria are satisfied:
    • Protocol uses a new vector, genetic material, or delivery method that represents a first-in-human experience, thus representing unknown risk.
    • Protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value.
    • Proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for local and federal regulatory bodies to evaluate the protocol rigorously.

I understand the idea that the RAC likely conducts a certain amount of review that is redundant.  Given the challenges facing other bodies with NIH-relevant ethics responsibilities, I would certainly understand if anyone took pause in response to the decision.  Especially since the NIH has yet to decide whether to follow another IOM recommendation – to replace the RAC with another body focused on gene therapy and other kinds of risky research.

Bioethics Commission Isn’t Waiting For Next Meeting To Issue BRAIN Report

The Presidential Commission for the Study of Bioethical Issues has a lot to say about the BRAIN Initiative.  So much that the Commission report will take at least two volumes.  The Commission released Volume One of Gray Matters: Integrative Approaches for Neuroscience, Ethics, and Society today.  It’s the seventh report of the Commission since it was formed in late 2009.

The report was prompted by a request from President Obama to “identify proactively a set of core ethical standards – both to guide neuroscience research and to address some of the ethical dilemmas that may be raised by the application of neuroscience research findings.”  The recommendations in Volume One of the report are focused on achieving a more explicit integration of ethics into neuroscience research throughout the life of a research program.  There are four main recommendations:

  1. Integrate ethics early and explicitly throughout research
  2. Evaluate existing and innovative approaches to ethics integration
  3. Integrate ethics and science through education at all levels
  4. Explicitly include ethical perspectives on advisory and review bodies

Of specific application to the BRAIN Initiative is the need to include professionals with expertise in ethics in advisory boards and similar entities conducting research in this area.

Volume Two will focus more on the social and ethical implications of neuroscience research, topics likely to appear on the agenda of the Commission’s next meeting.  As a hint of what may be in that report, the Commission notes four examples that demonstrate the need to better integrate ethics throughout the course of neuroscience research:

  1. Neuroimaging and brain privacy;
  2. Dementia, personality, and changed preferences;
  3. Cognitive enhancement and justice; and
  4. Deep brain stimulation research and the ethically difficult history of psychosurgery.

The Commission did not give a deadline for when Volume 2 would be ready, but it may provide some insight on that front during the June meeting in Atlanta.

Next Bioethic Commission Will Keep BRAIN on the Brain

Continuing from its last meeting (in February 2014), the Presidential Commission for the Study of Bioethical Issues will continue working on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in its June 9-10 meeting in Atlanta, Georgia.  An agenda is still forthcoming, but the Federal Register notice confirms that the Commission will have BRAIN as the main focus of the meeting, also covering relevant work in neuroscience.  The event will be webcast, so check the Commission’s website on June 9 and 10 for the relevant link.

I speculated recently that the successful in vivo replication of synthetic DNA with artificial base pairs would attract the Commission’s attention.  Without an agenda, it’s harder to be sure, but it seems that this development may have to wait for the next next meeting of the Commission.

In other developments, Commission staff are apparently going to examine some efforts to engage bioethical issues through plays.  Continue reading

New Base Pairs Provide Opportunity For Bioethics Commission

If I understand recent news reports correctly, possibilities for synthetic biology have widened dramatically.  While researchers have been able to ‘expand’ the capacity of DNA by introducing new base pairs in vitro, a letter (registration and/or payment required for full access) in the latest (May 9, 2014) edition of Nature claims to have developed a means of using a third base pair in vivo. 

Put another way, the synthetic base pairs were successfully replicated by a living cell, rather than just in a test tube.  That would allow for massive reproduction of compounds built with this new synthetic DNA, as living cells can reproduce entire strands of DNA, while methods like polymerase chain reaction (PCR) work on smaller sequences.  In vivo replication is also faster and more accurate compared to methods conducted outside the cell.

Arguably this is the most significant development in synthetic biology since the Presidential Commission for the Study of Bioethical Issues released its report on the topic back in 2010.  The recommendations on how to both nurture and monitor the emergent field of synthetic biology were relatively high level.  The researchers involved have already formed a company to support commercialization of the work, and at least one of the researchers is convinced that the possibility of synthetic DNA being released into the wild is zero.  Such claims deserve the kind of fact-checking that the Commission encouraged in its Recommendation 15.  Unfortunately, that’s the recommendation missing in this scorecard developed by the Wilson Center’s Synthetic Biology Project.

It would be nice if there could be a discussion on what this development means that ends up somewhere between “Stop!” and “There’s Nothing To See Here.”  Perhaps the Commission could nudge things at its next meeting (early June in Atlanta).

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.)

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.

Antidepressants and Brewers Yeast – Evolutionary Pharmacology

Baba Brinkman is back with another science rap.  The new one is titled Evolutionary Pharmacology.

As you might have gathered, this was done in connection with the lab of Ethan Perlstein.  In fact, the video is taken from on this earlier production that Perlstein put together to promote his independent lab (crowdfunded via Angelist).  Perlstein and his colleagues are working on orphan drug discovery and research related to those diseases.  The evolutionary pharmacology comes in because they are studying drug effects on yeast cells in order to better understand how well the drugs do (and/or do not) affect humans.

Either way, like the man says, don’t give Zoloft to infants.

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.

Lawsuits ‘R’ Us: 23andMe & Goldieblox

Two technology-oriented lawsuits of note for your weekend reading:

Besides the issues the Food and Drug Administration has with genetic sequencing firm 23andMe, the company has a lawsuit on its hands.  It’s a class action lawsuit filed in federal court.  Much like the FDA’s concerns, the class action focuses on how 23andMe represents the health screening tests it provide(d).  What I missed during the initial reporting is that there are two aspects to how the company markets its health screenings, both of which are suspect in the absence of rigorous proof of the validity of its tests.  Not only would consumers rely on the results for assessing their genetic health, but researchers using the company’s health databases depend on the reliability of that data.  If the company could not satisfy the FDA on the reliability of its tests, how can its customers depend on its data?

Apparently a letter of apology wasn’t enough to get GoldieBlox off the hook for how it used a Beastie Boys tune in a promotional video.  That GoldieBlox pre-emptively sued to establish a right to fair use certainly didn’t help.  The band has countersued the company, alleging systematic infringement of intellectual property – and not just their own.  In their Answer, the band asserts the following (page 7): Continue reading

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.