Venture Capital Giving Extra Scrutiny To Scientific Research

Two recent news items suggest that venture capital firms are taking extra care to make sure scientific research can properly inform their investment decisions.

A brief item in Science-Business Exchange (full article requires subscription) notes that at least one firm – Atlas Venture – has taken to hiring contract research organizations to independently validate academic science prior to making significant investment.  One could consider this simply conducting proper due diligence on the firms in which it may invest.  However, this could speak to the increases in retractions and other instances of scientific misconduct.  (That I saw this first via a Tweet from one of the folks behind Retraction Watch suggests the second possibility is at least plausible.)

Another venture capital firm will work with a scientific academy to help it assess future opportunities in late-stage biomedical companies.  The Academy of Medical Sciences in London will work with Park Vale Capital to connect its Fellows to investment advisors at the firm.  The Academy will receive a retainer to assist with administrative costs and receive a certain percentage of performance fees Park Vale receives on its investments.  In an effort to manage potential conflicts and avoid disclosures of proprietary or confidential information, the Academy will establish an oversight committee.  Relationships that go past the initial Academy-facilitated meetings will be handled through the researchers’ home institutions.

Both of these events are new in the area of venture capital.  Whether or not they will be the beginning of trends may depend on how well such arrangements work.  But at least in the case of Atlas Venture, these developments should remind us that the reliability of the research data and the processes behind it matter.  Put another way, while the moves could bring additional money to research, the additional scrutiny comes at least in part over increasing concerns about the quality assurance behind scientific research.

ProPublica Reminds Us That FDA Still Needs Repairs

The recent judicial rebuke over emergency contraception is just the latest example of the challenges the Food and Drug Administration (FDA) has had in getting its scientific and regulatory houses in order.  The kerfuffle over Plan B is different (but not an isolated incident) in that the interference in agency processes came from outside the FDA, rather than from within.  But the agency has a lot of work to do to deal with the conflicts, delays and struggles over drug and device approvals.  The agency is trying (the Commissioner did publicly disagree with the Secretary over Plan B), but it has a long way to go.

This week’s reporting by ProPublica (H/T Scientific American) focuses on the FDA’s relationships with contract drug testing companies.  The reporters recount how two companies were found to have conducted years of tests that were either unreliable or fraudulent.  As a result over 300 drugs needed to be retested, with at least 140 of those drugs already approved for sale.

None of the drugs were pulled from the shelves, even temporarily.  No public statements were made by the FDA about the retesting, even though the European Medicines Agency pulled seven drugs tested by one of the labs.  The FDA remains tight-lipped on the matter, and ProPublica has been able to identify only five drugs that were approved at least in part due to suspect tests of one of the two companies, Cetero (the other company is MDS Pharma Services).

(ProPublica has a number of other investigations worth looking into, many of which focus on medical and/or scientific topics.)

Clearly the FDA still has many challenges to tackle before it can effectively fulfill its regulatory obligations.  The bigger problem, as I see it, is an institutional culture that accepts glacially-paced efforts to correct errors, coupled with a complete lack of interest in informing the public.  I don’t envy Commissioner Hamburg’s task in trying to tame the agency.  I wish her the best of luck.

Brain and Brain! What Is BRAIN?

Those who get the allusion in the title, the program in question still stinks.

Announced at the beginning of April as one of the Obama Administration’s Grand Challenges, BRAIN (Brain Research through Advancing Innovative Neurotechnologies) is a new multidisciplinary, multi-agency program with roughly $100 million in the President’s recently announced budget for Fiscal Year 2014.  (Must note here the chronic failures of Congress in passing budgets make this funding far from a sure thing.)

Besides the federal research component (roughly $100 million from the National Institutes of Health, the Defense Advanced Research Projects Agency/DARPA, and the National Science Foundation) BRAIN will engage several non-governmental organizations to add over $100 million in additional research support.  The NGOs are the Salk Institute for Biological Sciences, the Kavli Foundation, the Howard Hughes Medical Institute and the Allen Institute for Brain Science.  The funding is anticipated to persist over a ten-year period.  So if the federal budget continues to be dysfunctional, there will still be some engagement in BRAIN.

Advisory Bodies Have BRAIN On Their Minds

Both the President’s Council of Advisers on Science and Technology (PCAST) and the Presidential Commission for the Study of Bioethical Issues will meet in 3 weeks.  Given recent developments, it seems likely they will both have a topic in common.

The Commission is scheduled to meet in Washington on April 30.  No agenda is available as of the day of this posting, but the Federal Register notice for the meeting indicated that incidental findings would be a focus.  Incidental findings have been on the Commission’s agenda for a while.  They represent data found from research and experiments that were beyond the scope of the research.  Typically this is an ethical challenge because informed consent of human subjects involved in such research is typically focused on the designed purposes of the research.

However, at the beginning of this month the President notified the Commission that he will formally request their input on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) program.  This is a new cross-agency (National Science Foundation, National Institutes of Health, Defense Advanced Research Projects Administration/DARPA) program intended to increase our understanding of how the brain functions; how we think, learn and remember.  The Commission will be asked to evaluate the ethical, legal and societal implications of the program and related developments in neuroscience.  Comparisons to the Human Genome Project have already been made.

Also interested in BRAIN is PCAST.  During the public session (there have always been non-public sessions of PCAST meetings, they just started acknowledging it in print) of its May 3rd meeting (draft agenda), PCAST will hear from the DARPA director and the National Science Foundation Assistant Director for Biological Sciences.  PCAST has held discussions on neuroscience before.  It is possible that PCAST may pursue a report on this topic, but that likely won’t be clear until at least after the upcoming meeting.  The other part of the public session (aside from the usual public comment session) will focus on the impact of technological advances on productivity and employment.

Should You Have A Choice To Know Your Incidental Findings?

Yesterday the American College of Medical Genetics and Genomics (ACMG) released a series of recommendations around incidental or secondary findings related to genetic tests (H/T ScienceInsider).  This attracted my attention for two reasons:

• The Presidential Commission for the Study of Bioethical Issues will be studying the ethical implications of incidental findings
• Two Scientific American blog posts appear to disagree  as to the meaning of the recommendations.  (This likely means the recommendations are just hard to effectively distill into short articles.)

Incidental findings refer to discoveries made in the context of looking for something else.  Consider it the testing equivalent of finding out that an experiment to test one hypothesis managed to prove another.  Genetically speaking this would be something like getting tested for abnormalities on one chromosome, and finding something odd on another chromosome.

The recommendations give additional details to a policy statement issued by ACMG in 2012.  But the recommendations move beyond an acknowledgement of incidental findings to an encouragement of seeking them out.

BRCA Patents Are Working Through The Courts Down Under

The Supreme Court will soon hear a case concerning Myriad Genetics and its patents of genes associated with breast cancer.  The main issue is whether or not the patenting of this genetic material for the purposes of lab tests is valid.

At least one other country is dealing with the same question through its courts.  Australia’s Federal Court ruled on Friday (H/T The Conversation) that the Australian patent for the BRCA1 gene is valid.  In short, that there was sufficient work done to create within the patented material an ‘artificial state of affairs’ that made the work patentable.  The Judge in the case did not consider it an easy decision.

“The real problem lies in knowing, or rather not knowing, what degree of human intervention is necessary before it can be concluded that the requisite artificial state of affairs exists. It is an especially difficult problem in the present case, not so much because the authorities provide no clear solution to it, but because the problem has an almost metaphysical dimension to it.”

Remember folks, I Am Not A Lawyer, and I’m not Australian.  The rest of the judgment provides useful Australian legislative history, suggesting that the country’s Parliament has considered, and may still, refine the requirements for patents related to genetic material.  As this is the first judicial action on the matter, the judgment is somewhat conservative – judicially speaking.  Recognizing that the legislature may yet act to change the legal landscape, the judge in this case seems disinclined to write new law – which is usually the case.

The Federal Court “shares first instance jurisdiction with the Supreme Courts of the States and Territories in the complex area of intellectual property (copyright, patents, trademarks, designs and circuit layouts).”  So the case started with this court, and there are possibilities for appeal.  The Applicants (plaintiffs) have until March 8 to file an appeal.  I would not be surprised if they did.

Supreme Court Wants To Hear More Cases Involving Genes

This blog has spent some time on the Myriad Genetics case, which should come before the Supreme Court in late March.  It focuses on patents connected to genetic testing.  Another genetics case is coming to the court, this one agricultural in nature (H/T Science – full article behind paywall).

Monsanto has developed a series of agricultural products that are pesticide-resistant.  Per their brand name, these seeds are “Roundup Ready” and can handle being sprayed by the Roundup pesticide.  The case coming to the Supreme Court comes from a matter involving the use of the progeny of these “Roundup Ready” seeds.  Bowman has purchased and used Roundup Ready soybean seeds and complied with Monsanto requirements for their use.  However, he also purchased and planted commodity seeds, many of which are the offspring of soybeans grown by Roundup Ready seeds.  The major question before the court concerns whether or not the patents on Roundup Ready soybean seeds apply to seeds that are produced by crops grown by the ‘original’ seeds.

Per SCOTUSBlog, Bowman vs. Monsanto Co. will have oral arguments on February 19.

NIH Reminds Us That Informed Consent Is Hard – Stem Cell Edition

When the Obama Administration made its policy decision to encourage federal funding for stem cell research, the National Institutes of Health (NIH) instituted a process for establishing ethical guidelines for how stem cell lines could be used in research.  There was some question at the time as to whether older cell lines could be used under the new guidance, due to concerns over effectively obtaining informed consent from the donors.

These concerns were well-founded then, and a recent review of existing stem cell lines has highlighted some lines that raise ethical concerns.  Conducted by research administrators at Rockefeller University and a bioethicist from The Hastings Center, the review was prompted by a survey that indicated many in-vitro fertilization clinics do not let donors know that their eggs could be used in stem cell research.  National Academies guidelines from 2005 require that gamete donors provide consent for use in stem cell research.

Of the 198 lines approved in the NIH stem cell registry at the time of the review, the researchers were able to determine that less than three-quarters of those lines can account for consent from the gamete donors.  Unfortunately, that cannot be done for about 30 lines, and those responsible for 19 lines did not respond to the survey.  The authors conclude:

“(1) Some NIH Registry lines were derived from embryos created using donor gametes. (2) Not all of these gamete donors provided specific consent for derivation of hESCs from resultant embryos. (3) Obtaining information about gamete donor consent is difficult.

“With such rapid advances occurring in stem cell research, it is critical that consent forms for donation of gametes to IVF refer not just to the possibility of future research use, but also to derivation of hESCs specifically. Also, information about the provenance of the hESC lines should be public and readily available. The hESC research community will be best served if their essential research materials—gametes and embryos —are donated by individuals who knowingly and willingly agree to the use of those materials in hESC research.”

Being able to assure proper consent for only 137 of 198 lines is not a satisfactory result, especially in an area of research where there is significant concern about the appropriateness of conducting research on embryos at all.  Greater transparency and thoroughness in following existing guidelines and requirements is one way to make the process of science much closer to the ideals that many wish to attribute to it.

Bioethics Commission Continues Its Work On Medical Countermeasures Research

On Monday and Tuesday in Miami the President’s Commission for the Study of Bioethical Issues will continue its work in a public meeting.  The agenda is a bit vague, but based on the Federal Register notice, the major topic on the agenda will be a continuation of the commission’s work on medical countermeasures research involving kids.  An example of such research would be determining the effective does of drugs to counteract anthrax exposure.  Given that the exposure to anthrax would be part of such research, there is notable risk to research subjects.  Research on children, as you might expect, requires additional caution to ensure that the subjects are adequately protected.

As noted at the Commission’s last meeting, the subject matter is challenging, and the Commission is breaking new ground.  The member discussion noted in the agenda is likely a continuation of the iterative process for generating an ethical framework for approaching this research.  However, I would anticipate the Commission remains on track for completing its report and issuing it within the next several weeks.

The meeting will be webcast, and I would expect there to be blog posts either during or shortly following Monday and Tuesday’s discussions.

I Was Wrong About When The Supreme Court Would Hear The Stem Cell Lawsuit

A little over a year ago I speculated as to when the Supreme Court would hear the lawsuit over the Obama Administration policy allowing  federal funds to be used to support embryonic stem cell research.  While my prediction of early 2013 may seem accurate based on last week’s action, in truth the Court had to have the case since last fall in order to review the matter and decide whether to hear the case.  The petition was filed by plaintiffs in October.

According to SCOTUSBlog, the Court gave no comment when it denied the petition to hear the case.  While the issue of NIH stem cell research policy could still be opposed, those not in favor will need to pursue their case through either Congress or the Executive Branch.  The latter is not happening during the current administration, and the former seems unlikely given the inability of Congress to pass much of anything.

Of course, the injunction that plaintiffs sough after filing the lawsuit back in 2009 didn’t last long in court.  While the resolution of this case reduces the uncertainty involved in pursuing federal money for embryonic stem cell research, I’m not sure that was much of a problem for researchers.