Report on "Egregious Academic Freedom Violation" at #UCDavis


Crossposting this here — posted originally on my lab blog.  NOTE – many updates down below at the bottom of page.

Wow — just got this email regarding Academic Senate issues at UC Davis and found out about this report on “Egregious Academic Freedom Violation” in relation to an issue at the Medical School. See email below as well as the report (see link) – starting on p62. It is a pretty sordid tale … (with some highlighting now added by me)


The email I received: 

*Sent on behalf of the Academic Senate Chair* 

Dear Academic Senate Members, 

On Friday, the Academic Senate Committee on Academic Freedom and Responsibility (CAFR) will be presenting their report, “Egregious Academic Freedom Violation” which begins on page 62 of the June 8 Representative Assembly meeting call (http://academicsenate.ucdavis.edu/ra/RA-Meeting-Call-2012-06-08.pdf). The Committee on Elections, Rules and Jurisdiction (CERJ) has put the recommendations of the CAFR report into the form of resolutions, which are attached. In order to be voted on by the Representative Assembly, the resolutions would have to be moved and seconded. We hope that the attachment will assist the Representative Assembly as its members review and consider CAFR’s recommendations.

Thank you.
From: Edwin M Arevalo
Sent: Friday, June 01, 2012 11:30 AM
To: ‘academic-senate@ucdavis.edu
Cc: Edwin M Arevalo

Subject: 2011-2012 Representative Assembly (RA): June 8 Meeting Call Notice


Importance: High

Dear Academic Senate Members,

This message is being sent on behalf of the Academic Senate Secretary, Ines Hernandez-Avila. Please see the following link (http://academicsenate.ucdavis.edu/ra/RA-Meeting-Call-2012-06-08.pdf) to access the Representative Assembly Meeting Call for Friday’s (6-8-12) meeting. You can also access RA information, meeting calls, and meeting summaries on the RA website (http://academicsenate.ucdavis.edu/repassembly.cfm).

Please remember that we no longer print hard-copies of the meeting call in an attempt to help save resources, financial and natural. We will be projecting the meeting call during the entirety of the meeting.

Note: The meeting call is longer than usual due to the insertion of the 35 page April 17 meeting summary (beginning on page 3) which includes the Chancellor’s State of the Campus speech.

Thank you,

Edwin M. Arevalo
Associate Director
Academic Senate Office, Mrak 402
University of California, Davis

(530) 754-7468

CAFR resolutions for June 8 2012 RA meeting.pdf


Here is the text from the report starting on p62

ACADEMIC SENATE, UC DAVIS DIVISIONCOMMITTEE ON ACADEMIC FREEDON AND RESPONSIBILITY

May 18, 2012
RE: Egregious Academic Freedom Violation Academic Senate:

The Committee on Academic Freedom and Responsibility (CAFR) has investigated a serious situation related to the academic freedom of an individual faculty member. By unanimous assent CAFR has found that the faculty member’s academic freedom was violated by precipitous and inappropriate retaliatory statements of disciplinary sanction and legal action in the hours and days following the publication of a professional expert commentary perceived by some to be against University interests. Further, the violation persists such that the professor works in fear for his job and has to withhold his professional knowledge from students and society for fear of further retaliation. University administrators involved in the case misunderstand the University’s policies and procedures regarding academic freedom and shared governance. The University’s fundamental mission is to discover new knowledge and to disseminate that to its students and to society at large. CAFR calls upon the Academic Senate to affirm that professors should not be subjected to disciplinary sanctions, legal action or threats thereof for writing scholarly publications and professional expert commentaries, and that evaluations of the intellectual honesty of such writings require due process through shared governance according to APM-015 and APM-016 without circumvention to the legal system or to unregulated administrative action. CAFR calls upon the administration to apologize and take concrete actions to learn from its missteps, as enumerated below .

Introduction and Procedures

According to Academic Senate bylaws, CAFR is charged with studying any conditions within the University that, in the judgment of the committee, may affect the academic freedom and responsibility of its individual members. When a faculty member brings forward a formal complaint, CAFR is obligated to investigate and write a report to the Academic Senate explaining our findings.

On November 22, 2010 a faculty member formally wrote an email to CAFR on the subject of “request for senate review” in which he sought advice about what he described as his being subjected to intimidation, threats, and harassment. The CAFR Chair undertook a preliminary investigation involving talking to several involved and peripheral parties as well as receiving documents in support of all perspectives. CAFR met to review the materials and discuss the situation. Before we could return formal advice, the Academic Senate Chair intervened to consult the Committee on Elections, Rules and Jurisdiction (ERJ) to evaluate whether this situation should be reserved for sole review by the Privilege and Tenure Investigative (PTI) committee. Although ERJ affirmed the independent and unfettered right of CAFR to proceed (as has occurred in similar situations UC systemwide in the past), the faculty member did not formally request that and CAFR informally advised the faculty member to contact PTI. All information regarding subsequent PTI activity is confidential and has been withheld from CAFR.

On December 21, 2011, the faculty member wrote to CAFR, “I would like to formally request a review of what I believe has been a blatant breach of my academic freedom.” CAFR informed the Senate Chair as well as the PTI Chair and then undertook an investigation. The investigation consisted of (a) reviewing the extensive past information from the complainant and from CAFR’s 2010 preliminary investigation, (b) inviting each direct party to meet with CAFR and then holding meeting with those who agreed, (c) reviewing a supervisor’s letter on behalf of one of the parties who declined to meet, (d) soliciting advice from the UC system-wide University Committee on Academic Freedom (UCAF), and (e) discussing the matter as a committee. These sources of information were used to write this report that presents the details of the situation and CAFR’s findings.

In preparing this report, a decision had to be made whether to redact the names of those involved. The faculty complainant agreed that his name could be used in the report. Given that information about the positions of the relevant parties is vital to laying out the events and complaint, it is impossible to completely hide the identities of those involved. The advice from experienced UCAF members was that the names of university officials need not be withheld, because they are in public positions that have accountability. Nevertheless, we have withheld the names of individuals other than the complainant, even though we cannot hold back the related information about their positions and actions, and it is difficult to write clearly without using gender-specific pronouns where necessary.

Chronology of Events and Related Facts

1. Professor Michael Wilkes, M.D., is widely credited with originating “doctoring” courses that are now used by 33 medical schools. Prof. Wilkes was recruited to the UCD medical school (UCDMS) from UCLA in part to create a four-year sequence of “doctoring” courses at UCDMS. Prof. Wilkes won a teaching award in 2010. Prof. Wilkes has been a medical reporter for the New York Times, ABC News, McClatchy newspapers, and other media where he has provided professional expert commentaries. Among other topics, he is a recognized expert on prostate cancer. He has co- authored scholarly articles and professional expert commentaries about prostate cancer screening in both peer reviewed journals and newspapers. In 2010 he was serving as Chair of the Consensus Committee for the Centers for Disease Control and Prevention. He has also served as an organizer for an international medical student exchange program, helping to host students from Hungary.

2. UCDMS faculty members advertised and subsequently held a public event at the UCD MIND Institute on September 28, 2010. The advertisement for the event most prominently states, “Prostate Defense Begins at 40”. There is also sizable text stating “Know Your Stats” with “About Prostate Cancer” in a very small font. There is also prominent text in red stating, “Attend a Free UC Davis Men’s Health Seminar”. The event was promoted with mention of special guest Guy McIntyre, a three- time Super Bowl participant, and former player for the San Francisco 49ers. It also has the symbols or nameplates for UC Davis Health System, AUAFoundation, and NFL.

3. Prof Wilkes first learned of the event and promotional campaign on September 16, 2010. The same day he wrote an email to the UCDMS Executive Associate Dean, the Associate Vice Chancellor for Strategic Technologies and Alliances, and the UCDMS Associate Dean for Curriculum and Competency Development. The email noted a concern about the presentation and suggested a lack of objectivity by the American Urological Association with regard to the prostate- specific antigen (PSA) test. Prof. Wilkes suggested it was contradictory for UCDMS to teach evidence-based medicine and concurrently host an event promoting the use of PSA, which he characterized as “far away from evidence-based”. The Executive Associate Dean wrote back the same day stating, “We cannot impinge academic freedom. maybe you need to be more interactive internally.”

4. Prior to the event, Prof. Wilkes investigated the advertisement and planned event. By his account, this consisted of (a) attempting to talk with the faculty members hosting it, (b) conversing with football player Guy Macintyre and researching his payment, and (c) attempting to obtain event materials.

5. Prof. Wilkes did not attend the September 28, 2010 event, but two medical students did attend and recorded it with an audio device in a set of 7-minute clips. The students provided Prof. Wilkes with the audio recordings. One student wrote that a video was played that the student deemed to be “unabashed marketing” and the student reported that “the urologists mentioned having a baseline PSA at age 40 for predicting lifetime risk of prostate cancer.”

6. On September 30, 2010 the San Francisco Chronicle printed an “Op Ed” article entitled “PSA tests can cause more harm than good” written by Prof Wilkes and a medical faculty colleague from another university. The article was edited by the newspaper to reduce the length (from 950 to 520 words), with the edited version provided to Prof. Wilkes the day before it was published using the standard editorial practices used by major newspaper outlets. An online version of the article was subsequently published on October 01, 2010 (see Appendix 1). The thesis of the article is that PSA tests can cause more harm than good, so men should be informed about the pros and cons of the tests to enable them to make informed decisions. The article provides several sources of evidence and professional judgments in support of the thesis. The authors used the event hosted by UCDMS faculty members to illustrate societal problems associated with PSA testing. The authors suggested and described possible financial motivations for the event, and in doing so they provided two caveats: (a) they can’t know why UC Davis offered the event and (b) they “wonder whether it just might have to do with money”. These are clear statements that their ideas are speculative commentary.

The Executive Associate Dean says that he received “multiple faculty complaints” about the article, but the timing of those complaints is unclear, so they are not assigned a sequence in the numbered chronology

7. At 7:02 am on the same day the article appeared in print (9/30/10), the Executive Associate Dean wrote an email to the UCDMS Associate Dean for Curriculum and Competency Development with copies going to the Associate Vice Chancellor for Strategic Technologies and Alliances and Prof. Wilkes in which he stated that (a) Prof. Wilkes would not be invited to continue as doctoring Instructor Of Record (IOR) after the academic year and (b) resources to support Prof. Wilkes’ Hungarian student exchange would be ceased after completing commitments to date. In a meeting with CAFR, the Executive Associate Dean acknowledged that he had read the San Francisco Chronicle article before he wrote this email.

10. At 8:30 am on October 2, the Associate Vice Chancellor for Strategic Technologies and Alliances wrote to Prof. Wilkes that the Executive Associate Dean “is clearly upset that the Men’s health issue is being played out in the paper and through the students rather than an academic debate or issue specific seminar as he would expect in a University.” [In a meeting between CAFR and the Executive Associate Dean, the Dean corroborated this when he said that his issue with Prof. Wilkes was not the debate about PSA, but rather the propriety of how Wilkes engaged in the debate].

11. At 10:45 am on October 2, the Executive Associate Dean refused a request by Prof. Wilkes to talk and informed him that further information would be coming about his “future with Doctoring 4 and with your position as Director global health for UCDHS.” UCDHS is the UC Davis Health System.

12. On October 5, Prof. Wilkes wrote an email to the faculty members who hosted the event in which he wrote, “I am sorry if this caused your team unnecessary angst” and explained that his original article was substantially cut and edited in a way that he felt created a more negative tone. He offered to take them to lunch and discuss educational opportunities. He also explained more about his scholarly position on PSA testing.

13. According to the UCDMS Executive Associate Dean, a meeting was held between the UCDMS Dean, the UCDMS Executive Associate Dean, and the Health System Counsel some time after the article was published. The UCDMS Dean made the decision to have the Health System Counsel write a letter to Prof. Wilkes.

14. The Health System Counsel wrote a letter to Prof. Wilkes in which he expressed the University’s concern about factual inaccuracies pertaining to UC Davis in the online version of the article. To CAFR’s knowledge, the Health System Counsel was not present at the event. The letter alleges that there are five false statements in the article, provides the statements, and describes reasoning as to why the statements are false. The origin of the scholarly analysis is not stated and there is no indication that a scholarly review was conducted. The letter then ends with the following paragraph, “The purpose of this letter is not to stifle legitimate public debate, academic freedom or policy advocacy about the role of PSA screening or broader issues- far from it. I am simply pointing out that there are numerous errors of fact in your article, that they were injurious to the University interests and reputation and thus potentially actionable under the law of defamation.”

15. Prof. Wilkes alleges that he was also told that his space was going to be re-assigned, although there is no documentation of that. In a meeting on November 30, 2010 between the CAFR Chair and the Executive Associate Dean, the intention of re-assigning Prof. Wilkes’ space was confirmed by the Executive Associate Dean.

16. As of May 1, 2012, none of the actions against Prof. Wilkes stated by the Executive Associate Dean (i.e. change in IOR, cessation of resources for Hungarian exchange, removal as Director of global health for UCDHS, and reassignment of space) have occurred.

Allegation of Violation of Academic Freedom

Prof. Wilkes alleges that his academic freedom has been violated and that he has been subjected to threats and harassment by the University as a direct response to the publication of his article in the San Francisco Chronicle. Prof. Wilkes alleges that the fact that the University has not carried out the actions against him to date is irrelevant in that the threatening proposed actions, including the threat of legal action against him, have not been withdrawn and there has not been any apology by the University for inappropriate behaviors that violated his academic freedom. As a result of the University’s actions against him, Prof. Wilkes is concerned about his employment status and concerned about his right to continue to freely pursue his scholarly research and professional expert commentary about ethics in medicine. The fear he feels and expresses has resulted in him have turning down opportunities for commentaries out of fear of further intimidation and loss of his job.

Key Factors in Defense of University

Removal of Prof. Wilkes’ IOR appointment: The Executive Associate Dean alleges that there was faculty and administrative discontent over Prof. Wilkes’ teaching, course management, and collegiality, and that these factors were the basis of the decision to remove him as IOR of Doctoring 3. There is widespread documented information that the Doctoring sequence as a whole had problems, so a Doctoring Task Force was established. This group was reviewing the courses in the series one at a time starting at Doctoring 1. In interviews and emails, different individuals pointed to very different concerns about the Doctoring sequence, so CAFR could find no clear consensus. As of March 2012 the Doctoring Task Force had yet to address Doctoring 3 or 4 as far as CAFR knew. According to a December 2010 email to the CAFR Chair from the Associate Dean for Curriculum- because the Doctoring Task Force would not be able to complete its work in time to make a decision about Doctoring 3 before it was to be taught the next time, the chairs of internal medicine, family medicine, and psychiatry met and recommended to the Executive Associate Dean that the IOR for Doctoring 3 be changed. The three chairs confirmed in an email to the CAFR Chair in December 2010 their agreement with this recommendation and alleged that their concerns go back to September 2009, even if the formal recommendation was not made until the time the San Francisco Chronicle article was published.

Removal of space: The Executive Associate Dean alleges that the space was needed by the home department that holds that space.

Removal of Hungarian student exchange of directorship of global health of USCHS: The Executive Associate Dean alleges that the program was being implemented poorly and that he had issued multiple warnings about how Prof. Wilkes was running the program.

Overall, the Executive Associate Dean alleges that the timing of the actions against Prof. Wilkes was purely coincidental. 

Letter from Health System Counsel: In a February 2012 letter to CAFR, the UC Davis Chief Campus Counsel provided the following information specifically pertinent to this review: (1) the Health System Counsel “letter in no way proposes or imposes disciplinary sanctions against Dr. Wilkes, (2) “Publicly broadcast false statements that injure the University’s interests and reputations are potentially actionable as a tort. Such a statement is a fact. It is not a threat and it is not a sanction.”, (3) “As indicated above in APM 016, faculty members remain subject to compliance with University rules and regulations, as well as laws, outside the scope of faculty discipline and ‘faculty are subject to appropriate administrative actions for failure to comply with such rules and regulations.’ ”; and (4) “The administrative action elected in this case was simply to provide information to Dr. Wilkes regarding the false information in his article and the potential legal exposure for broadcasting false information that is injurious to reputation. For these reasons, there was no requirement to first pursue disciplinary action against Dr. Wilkes under APM 016.”

Relevant Authorities

1. “The University of California is committed to upholding and preserving principles of academic freedom. These principles reflect the University’s fundamental mission, which is to discover knowledge and to disseminate it to its students and to society at large. The principles of academic freedom protect freedom of inquiry and research, freedom of teaching, and freedom of expression and publication.” (APM 010 ¶1).

2. “Members of the faculty are entitled as University employees to the full protections of the Constitution of the United States and of the Constitution of the State of California.” (APM-010, ¶3).

3. “The University seeks to provide and sustain an environment conducive to sharing, extending, and critically examining knowledge and values, and to furthering the search for wisdom. Effective performance of these central functions requires that faculty members be free within their respective fields of competence to pursue and teach the truth in accord with appropriate standards of scholarly inquiry.” (APM-015, ¶1).

4. Faculty have a constitutionally protected right to freedom of expression which includes the free exchange of ideas (APM-015, Part I).

5. “No disciplinary sanction for professional misconduct shall be imposed by the administration except in accordance with specified campus procedures adopted after appropriate consultation with agencies of the Academic Senate…” (APM-015, Part III A(1)).

6. “No disciplinary sanction shall be imposed until after the faculty member has had an opportunity for a hearing before the Divisional Committee on Privilege and Tenure…” (APM-015, Part III A(2)).

7. “While Administrative Officials may delegate many of their responsibilities, they cannot delegate accountability.” (UCD Administrative Responsibilities Handbook, p. 8).

8. New York Times Co. v. Sullivan, 376 U.S. 254 (1964) was a United States Supreme Court case which established the actual malice standard which has to be met before press reports about public officials or public figures can be considered to be defamation and libel. According to the actual malice standard, there has to be a reckless lack of investigation, which is a difficult standard to prove.

CAFR Findings
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With respect to the actions taken by the UCDMS administration, CAFR finds that Prof. Wilkes academic freedom has been violated. Prof. Wilkes was told that he would lose his IOR position for Doctoring 3, his space, and his directorship. That is undisputed. We can never know with 100% certainty that the actions by the Executive Associate Dean were a direct response to the San Francisco Chronicle article, but there is a very strong appearance of impropriety on the basis of several lines of evidence.

 
1) The timing of events is highly suspect beyond any reasonable doubt. The Executive Associate Dean admits the disciplinary email was written after reading the article and characterized the email as “intemperate.” The Executive Associate Dean agreed the email has an appearance of impropriety, based upon its close proximity to the timing of the article, even though he denies that the timing is connected. He characterized the email as “reflexive” and said if he had it to do over again, he would not have sent the email.

2) There is no evidence to indicate that Prof.Wilkes’ space was under review for reassignment prior to the date the article was published. Space is always a stressor, but by all accounts Prof. Wilkes has a well-funded research program that warrants the space he is allotted. There is no independent reasoning behind reassigning space at that specific moment in time.

3) There is no evidence to indicate that the Hungarian student exchange and Prof. Wilkes’ role as director of global health for UCDHS was under review or had reached a level of poor performance to necessitate cessation at that specific moment in time.

4) By all accounts, there was never any discussion to remove Prof. Wilkes as IOR of Doctoring 4, but the Executive Associate Dean sent a threatening email shortly after the article appeared that Prof. Wilkes should expect further information regarding his role in that course.

5) With regard to Doctoring 3, the information is highly conflicting and complex. On one hand, Prof. Wilkes won an award for his outstanding teaching in 2010 and is highly lauded by his students. The Executive Associate Dean described Prof. Wilkes to CAFR as “a gifted educator who uses technology well.” On the other hand, some faculty and administrators had concerns in 2010 that pre-dated the San Francisco Chronicle article. The UCDMS has in place numerous faculty bodies that play a role in curriculum and instructors, including an Executive Committee, a Committee on Educational Policy, a Doctoring Steering Committee that meets monthly, and a Doctoring Task Force. The fact that the Executive Associate Dean and the chairs of internal medicine, family medicine, and psychiatry abruptly decided to supersede the normal procedures of faculty shared governance and faculty oversight of administrative actions related to IORs is peculiar. Taking a decision on such a conflicted matter without faculty consultation and doing so on the very day a controversial article was published is at best very poor leadership, but more reasonably evidence of direct retaliation against Prof. Wilkes.

6) Removal of IOR, space, and a directorship would constitute disciplinary sanctions and stating these sanctions to a faculty member in response to alleged (by other faculty) or perceived (by the Dean) faculty misconduct requires that the administration proceed in accordance with specified campus procedures adopted after appropriate consultation with agencies of the Academic Senate (APM-015, Part III A(1)). No such procedures were followed regarding an evaluation of faculty misconduct. Instead, a final decision was given to Prof. Wilkes at 7:02 am on the very day the article was published.

7) The fact that none of the stated disciplinary actions has actually been carried out demonstrates that they were taken precipitously in the heat of the moment as a retaliatory action. The desire to act out against Prof. Wilkes at that moment trumped due process according to University policy and procedures for disciplining faculty for their conduct.

8) The fact that none of the stated actions has been formally withdrawn in writing (astheywere presented in writing) demonstrates that they are intended as a persistent threat. There was no indication given to CAFR that Prof. Wilkes’ space or directorship are under formal review. Therefore, continuing to leave these stated actions as they are serves no purpose other than to intimidate Prof. Wilkes.

With respect to the letter written by the Health System Counsel, CAFR finds that the University violated Prof. Wilkes’ academic freedom by acting precipitously to threaten potential legal action prior to a full and fair assessment of the facts or any establishment of “actual malice”. Contrary to the statement by the Counsel in his letter, CAFR finds that the purpose of the letter requested by Dean Pomeroy was precisely to stifle legitimate public debate and impinge on Prof. Wilkes academic freedom. A key line of evidence substantiating this judgment is that neither Dr. Wilkes’ co-author or the San Francisco Chronicle were sent letters by the Health System Counsel, even though they were mutually involved in writing and editing the article. Dr. Wilkes was not a sole author of the Op Ed. CAFR investigated and found out that only Dr. Wilkes was sent a letter. The UC Davis Chief Campus Counsel stated that the letter was intended to only be informational. If that was true, then why not send that information to all parties involved, since they would all bear equal jeopardy? The fact that the letter was only sent to Dr. Wilkes is an inconsistency that presents a strong appearance of impropriety on the part of the Health System Counsel if the goal truly was to be informative. Furthermore, the defamation standard for showing actual malice is high and notably the letter from the Health System Counsel does not address the topic of actual malice, only the presentation of perceived false statements. That is a surprising omission if the claim of defamation is to be taken seriously as informational instead of as a threat. Establishing actual malice would require a more substantial effort than undertaken by the Health System Counsel to determine what prior investigation Dr. Wilkes had undertaken. CAFR was able to establish that Dr. Wilkes did try to investigate the event prior to its occurrence and he did speak to the former football player.

By definition, a threat is a statement of an intention to inflict damage in retribution for something done or not done. The words in the letter exactly conform to that definition, so it is certainly a threat. When a University lawyer sends an official letter on University letterhead to a professor (excluding his co-author and newspaper editor from similar action) stating that the professor’s academic writings or professional expert commentary are potentially actionable under the law and the letter fails to provide the key information that makes the professor’s writing “actual malice”, then that is absolutely a threat. In fact, since most faculty do not have their own legal counsel, it is essentially a gamble preying on the ignorance of faculty. Further, the letter had an immediate chilling effect upon Prof. Wilkes’ willingness to engage in his long-time established practice of providing professional expert medical commentary for various reputable publications, and also his willingness to engage medical students in important teaching dialogue. The effect of the letter has been to suppress Prof. Wilkes’ academic freedom and to instill in him a fear of legal retaliation and unemployment if he presents scientifically sound, but perhaps controversial material. This violation was carried out by the UCDMS Dean in demanding the letter be written and the Health System Counsel for writing it

1) Beyond any doubt, Prof. Wilkes is a scholar with expertise on prostate cancer. APM-010 and APM-015 present no limitation as to the venues, format, or content of scholarly publication and professional expert commentary. Scholarly publications commonly include professional judgments and speculations, which are in due course subject to scholarly discussion and/or critique. Consequently, any article Prof. Wilkes writes on prostate cancer, drawing on any information related to that topic, is scholarly and pertains to his professional obligations acting as a faculty member. University oversight and discipline of faculty as pertains to scholarly writings is governed by APM-015 and 016. Therefore, by circumventing the required venues for oversight and discipline of faculty scholarship, the University violated Prof. Wilkes’ academic freedom by sending him a threatening letter on legal affairs letterhead in place of pursuing appropriate investigation and potential discipline.

2) The stated purpose of the Health System Counsel’s letter was to take issue with the truth of statements made in the article. That is inherently a scholarly discussion, not a legal one. If the UCDMS Dean wanted to address that, then the Academic Senate is the body charged with evaluating the merit of scholarship. The Health System Counsel is not a scholar on prostate cancer and is not qualified to render a judgment as to the veracity of statements in the article, which is exactly what he did in the letter. The fact that the letter’s stated purpose was to render such scholarly judgment is the strongest evidence that the topic at hand was in fact Wilkes’ intellectual honesty. Contrary to the claim by the Chief Campus Counsel in the subsequent letter to CAFR, the topic of intellectual honesty is definitely covered by APM- 015, which states the ethical principle that professors “accept the obligation to exercise critical self-discipline and judgment in using, extending, and transmitting knowledge. They practice intellectual honesty.” The letter by the Health System Counsel directly accused Prof. Wilkes of violating these ethical principles. As a result, the letter has everything to do with faculty conduct. Therefore, by circumventing the required venues for oversight and discipline of intellectual honesty, the University violated Prof. Wilkes’ academic freedom by sending him a threatening letter on legal affairs letterhead in place of pursuing appropriate investigation and potential discipline.

3) In the letter by the Chief Campus Counsel that defended the original letter, the claim is made that faculty members remain subject to compliance with University rules and regulations and that faculty are subject to appropriate administrative actions for failure to
Representative Assembly Meeting Call 6/8/2012 comply with such rules and regulations. Indeed, if a faculty member fails to return a library book they may be disciplined and so on. Unfortunately, neither the original letter to Prof. Wilkes nor the subsequent letter by the Chief Campus Counsel state any specific University policy as having been violated. In fact, no one has ever written or stated a University policy that Prof. Wilkes violated. Therefore, that defense of the letter is baseless. 

4) Both the Health System Counsel and the Chief Campus Counsel stated that publicly broadcasting false statements that injure the University’s interests and reputations are potentially actionable as a tort. However, the University did not convene a scholarly evaluation by peers in the Academic Senate to determine if in fact any false statements were made or present information to show that the statements rose to the high standard of “actual malice”. The choice to not send a warning letter to the San Francisco Chronicle and the other author is indicative of the weakness of the potential action. According to legal sources, the fact that the allegedly defamatory communication is essentially true is usually an absolute defense; the defendant need not verify every detail of the communication, as long as its substance can be established. The defendant in this case would be one of the nation’s foremost experts on medical ethics- who better to make professional judgments in a public article? This goes to the heart of there being some possibly mistaken statements in the article, as the occurrence of some false statements do not rise to the standard of defamation- a fact that the Counsel chose not to reveal to Prof. Wilkes. Furthermore, legal sources indicate that a public official or entity (even non-governmental) must prove that a libelous statement “was made with ‘actual malice’—that is, with knowledge that it was false or with reckless disregard to whether it was false or not” (New York Times v. Sullivan, 376 U.S. 254, 84 S. Ct. 710, 11 L. Ed. 2d 686 (1964)). Neither Counsel made an allegation of actual malice in their letters and it was clear in our communications that Prof. Wilkes was deeply concerned with getting to the truth. CAFR has established that Prof. Wilkes did conduct some investigation about the UCDMS event prior to its occurrence and he was certainly already among the foremost experts on the topic of prostate cancer. Simply not attending the event and being precluded from receiving the powerpoint presentation in advance do not rise to the standard of actual malice. Consequently, it is very difficult for a plaintiff to prevail in a libel action. Knowing that and without providing Prof. Wilkes with any actual information about defamation and the “actual malice” standard, the only reasonable conclusion is that the sole value in making a statement of this nature to a professor is to intimidate and threaten. The failure to follow appropriate procedures, the precipitous timing of the letter, and the low potential for achieving the “actual malice” threshold demonstrate the punitive purpose of the letter as a threat to harm and stifle Prof. Wilkes.

5) The fact that the University would take the position that it is appropriate to take legal action against a professor whose scholarly writing or professional expert commentary is perceived as injurious to University interests and reputation is an unprecedented affront to academic freedom and the people of California. APM-010 states that the University’s fundamental mission is to discover new knowledge and to disseminate it to its students and to society at large. APM-010 is intended to protect scholarly publication without caveat as to the subject matter of the scholarship. Circumventing University policy and procedures that serve the University’s fundamental mission by precipitously launching legal action or threats thereof is an outrageous abuse of power that undermines the standing of the University in society.

The University ought to abide by its own policies and seek to address allegations of faculty misconduct through its internal procedures prior to threatening or taking legal action.

Conclusions

CAFR finds that Prof. Wilkes was and continues to be subjected to egregious threats and unfounded potential disciplinary sanctions by UCDMS administrators and the UCD Health System Counsel. These threats and potential disciplinary sanctions stem from the perception of faculty misconduct in terms of intellectual dishonesty related to statements made in a newspaper Op Ed he wrote in which a University event was used as a case study to illustrate questionable practices in the health sector. UCDMS administrators stated that they would have preferred that Prof. Wilkes keep the matter internal, but in fact there is no limitation on faculty in presenting their scholarship and professional expert commentary publicly. In fact, faculty are encouraged in policies and practices to demonstrate to students real-world applications of the topics of their scholarship and to get involved in societal matters to bring their professional capabilities to bear on important topics of the day. That is exactly what Prof. Wilkes did. It is not for CAFR to evaluate the merits of the contents of Prof. Wilkes’ article, and neither is it for the Health System Counsel or administrators to decide either. Assessment of faculty scholarship, including issues related to faculty conduct are governed by shared governance procedures in APM-015 and APM-016. The timing of the stated sanctions immediately following the publication of the article and other evidence indicate a strong appearance that the two were linked. Further, the emails and letters by UCDMS administrators and the Health System Counsel were so precipitous, beginning with the strongest sanctions at 7:02 am on the very day of publication, that they were without rational scrutiny and lacked evaluation of the facts. The Health System Counsel letter arrived just 19 days after the publication and purports to present a thorough scholarly rebuttal, but without having followed any appropriate procedure for faculty assessment of scholarly content. The letter was only sent to one Op Ed author and failed to present and explain the basis for actual malice. Writing on the letterhead from legal affairs to tell Prof. Wilkes that his scholarly writing was potentially actionable under the law of defamation was a blatant threat intended to damage him and in fact there is little legal potential for successfully pursuing action against a foremost national scholar on the topic of his scholarship to meet the standards for defamation. Finally, the contention that the University may take legal action against faculty for their scholarship or professional expert commentary any time it is perceived to injure University interests and that the University may do so without any faculty consultation regarding matters related to faculty misconduct renders University policy and procedures impotent and alerts society that the University cannot be trusted as a truthful and accountable purveyor of knowledge and services. It is far more injurious to University interests that Prof. Wilkes’ scholarship is being stifled through unjust and unreasonable threats of legal action and potential disciplinary sanctions than it is to have society know what Prof. Wilkes’ professional judgment is about PSA tests and what his speculations are about any associated University financial motivations.

CAFR recommends to the Academic Senate that the following actions be taken:

1) The Representative Assembly vote to affirm the academic freedom right of Prof. Wilkes and all other faculty to publish scholarly articles and professional expert commentaries that address ethics and societally relevant critiques.

2) The Representative Assembly vote to express severe disapproval in the perspective that the University may take legal action against professors whose scholarly publications or professional expert commentaries may be perceived by University administrators to injure University interests.

3) The UCDMS Dean, UCDMS Executive Associate Dean and Health System Counsel must within 6 months all promptly and publicly accept responsibility for serious errors of judgment, write individual apologies to Prof. Wilkes, and rescinding all disciplinary actions stated, proposed, or taken against Prof. Wilkes.

4) The UCDMS Dean must within 6 months take concrete steps to prevent future violations of academic freedom rights, including training administrators, their staff, and faculty on academic freedom rights.

5) The UCDMS Dean must report back to the Academic Senate 6 months hence about what training activities have been done.

Unanimous Assenting Committee Members: 

Moradewun Adejunmobi, Professor
James Beaumont, Professor Emeritus
Eric Nelson, Graduate Student Representative 
Gregory Pasternack, Professor, Chair 
Adela De La Torre, Professor Jane-Ling Wang, Professor

Appendix 1: San Francisco Chronicle Online Article

PSA tests can cause more harm than good

Michael Wilkes,Jerome Hoffman Friday, October 1, 2010

UC Davis just announced a seminar for the public on “men’s health.” That title notwithstanding, the program appears to be entirely about prostate cancer and in particular about the prostate specific antigen screening test. Prostate cancer can be devastating, and the PSA is intended to find cancer early – in time to do something about it.

If only it were that simple. Research has shown that there are steps people can take to improve the quality and length of their lives, even before they’re having any symptoms. (That’s what “screening” for disease is.)

Unfortunately, though, the devil’s in the details, and many possible screening programs turn out not to do any good – and in fact some tests like PSA cause harm. That’s why virtually all expert public health panels do not recommend the PSA test.

A blood test that isn’t accurate can fail to find disease that’s present, leading to false reassurance. It can also report disease when it’s not really there, leading to unnecessary use of other tests (like biopsy) that are not so benign. Perhaps most concerning, the PSA test frequently identifies something that qualifies as cancer under a microscope but acts nothing like cancer in real life. That is to say, the large majority of PSA-discovered “cancers” would never cause any problem whatsoever if they went undetected.

But because doctors can’t tell whether one of these “cancers” is benign (as it usually is), or might occasionally be one of the bad actors, finding something through screening invariably leads to treating it.

Most of the men so treated would have been just fine if they never knew about the cancer. But when they’re treated (whether with surgery, radiation or chemotherapy), the majority suffer really life- affecting effects, such as impotence and/or incontinence. That’s why both of the two very large trials of PSA screening published in 2009 found no (or at most a tiny) benefit, but a great deal of harm.

Sadly, most men are never told the facts about the test, nor are they encouraged to make their own informed decision. The UC Davis course doesn’t even acknowledge a problem with prostate cancer screening. Its expert presenters – including two urologists and a professional football player (!) – will tell you that you need to “know your (PSA) statistics” beginning at age 40. Contrast this to the comments of Dr. Richard Ablin, the inventor of the PSA test, who has publicly called it “a hugely expensive public health disaster,” with accuracy “hardly better than a coin toss.”

We can’t say why UC Davis offers this course that ignore scientific evidence, but we wonder whether it just might have to do with money. Testing for and treating PSA-identified cancer is a large part of the practice of many urologists so it may not be surprising that urology groups take a far more positive stance on the test than almost any other doctors. They also fund a pro-PSA lobby that now includes the National Football League.

Health care spending is threatening to wreak greater and greater havoc on our economy. That’s not to say we shouldn’t invest in treatments that lead to improved health, even when they’re expensive.

And UC Davis, the NFL and surgical device companies have the right in our society to promote events in order to increase their profits. But we worry when companies and doctors with a conflict of interest sponsor what could be considered an infomercial endorsement to unsuspecting men without telling them they might end up being harmed as a result of a simple PSA blood test.

Michael Wilkes is a professor of medicine at UC Davis, and Jerome Hoffman is a professor of emergency medicine at the University of Southern California. Both are researchers/consultants for the U.S. Centers for Disease Control and Prevention.

http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2010/10/01/EDET1FLK3B.DTL This article appeared on page A – 14 of the San Francisco Chronicle





UPDATE: Some links of relevance
UPDATE 2: Some new links (6/8)
  • UC removes “In the media” page which linked to the Inside Higher Ed. story.
  • UC Davis Academic Senate passes three resolutions in relation to this case.  See here for full text.

Report at #UCDavis on “Egregious Academic Freedom Violation” #Yuck

Wow — just got this email regarding Academic Senate issues at UC Davis and found out about this report on “Egregious Academic Freedom Violation” in relation to an issue at the Medical School.

See email below as well as the report (see link) – starting on p62. It is a pretty sordid tale …

*Sent on behalf of the Academic Senate Chair*

Dear Academic Senate Members,

On Friday, the Academic Senate Committee on Academic Freedom and Responsibility (CAFR) will be presenting their report, “Egregious Academic Freedom Violation” which begins on page 62 of the June 8 Representative Assembly meeting call (http://academicsenate.ucdavis.edu/ra/RA-Meeting-Call-2012-06-08.pdf).  The Committee on Elections, Rules and Jurisdiction (CERJ) has put the recommendations of the CAFR report into the form of resolutions, which are attached.  In order to be voted on by the Representative Assembly, the resolutions would have to be moved and seconded.  We hope that the attachment will assist the Representative Assembly as its members review and consider CAFR’s recommendations.

Thank you.

From: Edwin M Arevalo
Sent: Friday, June 01, 2012 11:30 AM
To: ‘academic-senate@ucdavis.edu
Cc: Edwin M Arevalo
Subject: 2011-2012 Representative Assembly (RA): June 8 Meeting Call Notice
Importance: High

Dear Academic Senate Members,

This message is being sent on behalf of the Academic Senate Secretary, Ines Hernandez-Avila.  Please see the following link (http://academicsenate.ucdavis.edu/ra/RA-Meeting-Call-2012-06-08.pdf) to access the Representative Assembly Meeting Call for Friday’s (6-8-12) meeting.  You can also access RA information, meeting calls, and meeting summaries on the RA website (http://academicsenate.ucdavis.edu/repassembly.cfm).

Please remember that we no longer print hard-copies of the meeting call in an attempt to help save resources, financial and natural.  We will be projecting the meeting call during the entirety of the meeting.

Note: The meeting call is longer than usual due to the insertion of the 35 page April 17 meeting summary (beginning on page 3) which includes the Chancellor’s State of the Campus speech.

Thank you,

Edwin M. Arevalo

Associate Director

Academic Senate Office, Mrak 402

University of California, Davis

(530) 754-7468

CAFR resolutions for June 8 2012 RA meeting.pdf

Does phylogeny matter? (In Eco-Evo meta-analyses) … Apparently, yes, but it depends.

As many may know – I am pretty obsessed with the uses of phylogeny in biological studies.  In fact, one could say this has driven almost all of my work.  Thus when an email went around a little bit ago about an article for a journal club at UC Davis where the title begins with “Does phylogeny matter?”, well, I had to take a look.  Alas, I was a bit worried when I saw the article was in Ecology Letters because I am at home and was not sure about access policies for this journal.

But I was pleasantly surprised to get full access without any library – VPN login to the following article: Does phylogeny matter? Assessing the impact of phylogenetic information in ecological meta-analysis – Chamberlain – 2012 – Ecology Letters – Wiley Online Library.  I cannot figure out WHY it is freely available right now, nor how long it will be, but I took the chance to look the article over.

And I was even more pleasantly surprised to look over the article.  Many meta-analyses can seem forced – if not almost unbearable to look through.  But this one is very well done.  Basically they did a massive comparison of conclusions that one could reach when one either does or does not take into account the phylogenetic non-independence of taxa when conducting meta-analyses in evo-eco studies.  They searched published literature for meta-analyses and then .. well I will use their words here (from the end of their introduction):

Herein, we re-analyse datasets from previously published meta-analytic studies, comparing results of traditional and phylogenetic meta-analyses. In addition, we attempt to explain variation in the effect of phylogenetic information on meta-analytic outcomes by examining characteristics of phylogenies. We ask: (1) how does accounting for phylogenetic non-independence change results of individual meta-analyses? and (2) across datasets, what characteristics of phylogenies explain changes in effect size for phylogenetic vs. traditional meta-analyses? As a complement to our main questions, in Appendix A, we also ask (3) how does accounting for phylogenetic non-independence affect model fit of individual meta-analyses? and (4) across datasets, what characteristics of phylogenies explain variation in the relative fit of phylogenetic meta-analyses? Despite the many compelling reasons to incorporate phylogenetic information into meta-analyses that involve multiple species, investigators often use model comparison criteria, such as Akaike’s Information Criterion (AIC) to assess fit of phylogenetic vs. traditional meta-analytic models. We found a clear bias in relation to phylogeny size for one of the two methods currently used to quantify relative model fit (Q-based AIC), thus our findings have important implications for meta-analysts using such model comparisons (see Appendix A for details).

And the key conclusions are

Here, we have shown that incorporating phylogenies influences ecological meta-analysis outcomes, in many cases changing whether the observed effect size differs significantly from zero. We also show that the degree of difference between traditional and phylogenetic meta-analyses depends on key characteristics of phylogenies. Despite this potential complication, we strongly recommend incorporating phylogenetic information into ecological meta-analyses to account for species non-independence.

They also offer up three main recommendations for consideration

To conclude, we outline three recommendations for the use of phylogenetic meta-analyses in ecology and evolutionary biology:

  1. Use phylogenetic meta-analysis, but note that some response metrics are less likely to be affected by phylogenetic methods.
  2. Include as many species as possible.
  3. Be aware that phylogeny shape may influence meta-analytic outcomes. 

Definitely worth a look …

Chamberlain, S., Hovick, S., Dibble, C., Rasmussen, N., Van Allen, B., Maitner, B., Ahern, J., Bell-Dereske, L., Roy, C., Meza-Lopez, M., Carrillo, J., Siemann, E., Lajeunesse, M., & Whitney, K. (2012). Does phylogeny matter? Assessing the impact of phylogenetic information in ecological meta-analysis Ecology Letters, 15 (6), 627-636 DOI: 10.1111/j.1461-0248.2012.01776.x

ResearchBlogging.org

Fulbright Post Doc Fellowships abroad in Israel

Fulbright Israel to award 8 Post-Doctoral Fellowships to Americans for research in Israel, 2013/2014-2014/2015.

The Fulbright Israel Program, managed by the United States-Israel
Educational Foundation (USIEF), offers post-doctoral fellowships, which
complement stipends provided by Israeli host institutions.
This program is open to American post-doctoral researchers in all academic disciplines.
For full announcement: http://www.fulbright.org.il/index.php?id=1317
and to review the online application material: http://www.cies.org/us_scholars/us_awards/Application.htm

Many thanks in advance,
Ilan Amit
Fulbright Israel
http://www.fulbright.org.il

Overselling genomics award #7: Ron Davis & Forbes for PR presented as "essay"

Wow.  Just saw this tweet by Dan Vorhaus:

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So I decided to check it out. The piece is titled It’s Time to Bet on Genomics and it is, well, just completely in appropriate.  Sure – it does take on an article that itself was over the top in downplaying the power of genomics (see Erika Check Hayden’s article about that issue here).  But then Davis goes on to write about a company founded by an ex post doc of his for which Davis is one of the advisors (he does kindly let us know this, but still …).  And what he writes he is a big big pile of fluff with no evidence presented.  Among the lines in the “essay” I find disturbing:

  • One of the most interesting of these is being developed by Genophen
  • Genophen’s application is rather breathtaking in its ambition.
  • Genophen’s “risk engine”—a simple term for some very complex data mining and computer modeling—will map your risk factors against the world’s vast library of medical research and then offer up a personalized set of behavior and treatment recommendations that can help you reduce those risks . . .  and even prevent disease itself.
  • We are now at the point where genomics-enabled medical technology can run various what-if scenarios and show you whether diet, exercise, medication, or some other factor or combination of factors has the greatest statistical likelihood of reducing that risk. The information can then be visually displayed through charts and graphs and made available to patients and their doctors via secure web-based portals.
  • But instinctively I believe it to be true, and anecdotally Genophen’s first trial provided some confirmation.
  • “The trial changed my life,” one female participant who wishes to remain anonymous told me.

All of this without any link to a paper, without any data, without any real details.  Shameful.  Not saying genomic medicine does not have a lot of promise.  But this “essay” is so excessively focused on PR for one company that there is no reason to have any faith in anything said in it.  I am therefore giving Ron Davis and Forbes my coveted Overselling Genomics Award (#7).  Plus I think Forbes deserves some sort of award for “Publishing PR” but I will have to think one of those up.  This piece almost certainly never should have been published at Forbes.Com without many many more caveats.  Yuck.

UPDATE – here is a screenshot from the Forbes Web site.  It is marked as “Forbes Leadership Forum” … hard to tell whether it is meant as an essay, editorial, op-ed, or what.

Diversity (of speakers, participants) at meetings: do something about it

Some unformed thoughts here but here goes.

Every so often I see a conference announcement and am annoyed by the XY/XX excess for the speakers.  Some recent examples

And more.

Now – I complain about this here and there on Twitter and the like

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But I felt that this needed a blog post to not get lost in the Twitter stream.  So here it is.

I note – I have posted about this issue previously: A conference where the speakers are all women? | The Tree of Life and for conference for which I am involved I have been trying very hard to work on the speaker diversity (not just XX vs XY, but age, career status, ethnicity, etc).  And it certainly can be difficult to make sure that diversity is there.  But the meetings I list above are pretty egregious.  The Genome Canada one features seven major speakers – all white males.  Yes, they are all big names.  But in biology, where women are reasonably well represented, it suggests a bias to me if a meeting can somehow only manage to invite and/or attract all senior, white, XYs to be major speakers.  Not sure what that bias is and it could be different in each case –  could be who is invited – could be the field itself – could be timing/nature of the meeting – could be something to do with families (e.g., perhaps women are invited but are more likely to feel like limiting travel due to roles in child care).

Also I note – biases are not necessarily affecting any one gender or ethnic group.  For example, I have generally stopped going to meetings/conferences that are on weekends and I have also stopped going to meetings/dinners after 6 PM because I do not want to skip out on time with my family.

So here is a plea.  Next time you are involved in organizing a meeting – make some effort to have a strong representation of diversity of speakers and participants.  For example, if you invite lots of women for example and all say no – try to figure out why and see if you can fix the issue.  Offer travel fellowships for students.  Offer child care or child activity options (even if you cannot pay for it – at least make it easy for people).  Make sure to advertise/promote the meeting to groups/institutions with a high representation of underrepresented groups.  Don’t give up if your first efforts don’t work.  Sometimes it can be difficult to make sure diversity levels are high.  But keep trying … it will help make the conference better and also will help the field in general …

For other posts on this topic see

Dubious Press Release from Cedars-Sinai linking Irritable Bowel Syndrome (IBS) and Bacteria in Gut

Quick one here.

Not impressed with this press release from Cedar-Sinai: Dr. Pimentel links IBS and gut bacteria – Cedars-Sinai (see other variants of it here: Daily Disruption – Cedars-Sinai Study Links Irritable Bowel Syndrome (IBS) and Bacteria in Gut and here: Irritable bowel syndrome clearly linked to gut bacteria).

Among the things that bug me here:

  • They don’t include a link to the paper or even provide a citation
  • They claim that culturing microbes is the “gold standard” for connecting bacteria to the cause of this disease.  AND they imply this is the first method to use culturing to study the disease.  Both notions are wrongheaded.  
  • They confuse cause of IBS and symptoms.  They say that b/c antibiotics help reduce symptoms, therefore, bacteria cause the disease.  Really?  So then fevers must cause things like malaria and flu because ibuprofen helps reduce symptoms right?
  • At some point it might be nice to mention that the MD behind the new study has also been pushing the idea that IBS is caused by bacterial overgrowth for many years both in a book and via a testing company though it is unclear what his association with the company is.  I note – ads for the book claim ” In addition, Dr. Pimentel presents a simple treatment protocol that will not only help you resolve your IBS symptoms, but will also prevent their recurrence.”  So – apparently he already had a cure BEFORE the new study was even done.  I general I am skeptical of papers that show evidence for something coming from someone who apparently already “knew” the answer.

Of course, I am not saying IBS is NOT caused by bacterial overgrowth as they claim.  But I can say this – PRs like this make me skeptical that anything new was done in this current publication.

Nice Collection from Diane Dawson: Open Science and Crowd Science: Selected Sites and Resources

Quick post here – already posted to Twitter and wanted to make sure this one was seen by people who read this blog but don’t follow me on Twitter.

There is a nice compilation/commentary/review from Diane Dawson titled Open Science and Crowd Science: Selected Sites and Resources.  It is in the journal “Issues in Science and Technology Librarianship” (which I note – is a new one to me).  It has a lot of useful resources and comments about various open science activities on the web.  Definitely worth checking out.

Yum – Carbon monoxide, worms, bacteria – all together – what could be better

Just a quick one here pointing people to a paper and some stories relating to work by Nicole Dubilier on the worm Olavius algarvensis and it’s chemosynthetic symbionts.

Guest post: Story Behind the Paper by Joshua Weitz on Neutral Theory of Genome Evolution

I am very pleased to have another in my “Story behind the paper” series of guest posts.  This one is from my friend and colleague Josh Weitz from Georgia Tech regarding a recent paper of his in BMC Genomics.  As I have said before – if you have published an open access paper on a topic related to this blog and want to do a similar type of guest post let me know …

—————————————-
A guest blog by Joshua Weitz, School of Biology and Physics, Georgia Institute of Technology

Summary This is a short, well sort-of-short, story of the making of our paper: “A neutral theory of genome evolution and the frequency distribution of genes” recently published in BMC Genomics. I like the story-behind-the-paper concept because it helps to shed light on what really happens as papers move from ideas to completion. It’s something we talk about in group meetings but it’s nice to contribute an entry in this type of forum.  I am also reminded in writing this blog entry just how long science can take, even when, at least in this case, it was relatively fast. 


The pre-history The story behind this paper began when my former PhD student, Andrey Kislyuk (who is now a Software Engineer at DNAnexus) approached me in October 2009 with a paper by Herve Tettelin and colleagues.  He had read the paper in a class organized by Nicholas Bergman (now at NBACC). The Tettelin paper is a classic, and deservedly so.  It unified discussions of gene variation between genomes of highly similar isolates by estimating the total size of the pan and core genome within multiple sequenced isolates of the pathogen Streptococcus agalactiae.  

However, there was one issue that we felt could be improved: how does one extrapolate the number of genes in a population (the pan genome) and the number of genes that are found in all individuals in the population (the core genome) based on sample data alone?  Species definitions notwithstanding, Andrey felt that estimates depended on details of the alignment process utilized to define when two genes were grouped together.  Hence, he wanted to evaluate the sensitivity of core and pan geonme predictions to changes in alignment rules.  However, it became clear that something deeper was at stake.  We teamed up with Bart Haegeman, who was on an extended visit in my group from his INRIA group in Montpellier, to evaluate whether it was even possible to quantitatively predict pan and core genome sizes. We concluded that pan and core genome size estimates were far more problematic than had been acknowledged.  In fact, we concluded that they depended sensitively on estimating the number of rare genes and rare genomes, respectively.  The basic idea can be encapsulated in this figure:

The top panels show gene frequency distributions for two synthetically generated species.  Species A has a substantially smaller pan genome and a substantially larger core genome than does Species B.  However, when one synthetically generates a sample set of dozens, even hundreds of genomes, then the rare genes and genomes that correspond to differences in pan and core genome size, do not end up changing the sample rarefaction curves (seen at the bottom, where the green and blue symbols overlap).  Hence, extrapolation to the community size will not necessarily be able to accurately estimate the size of the pan and core genome, nor even which is larger!

As an alternative, we proposed a metric we termed “genomic fluidity” which captures the dissimilarity of genomes when comparing their gene composition.

The quantitative value of genomic fluidity of the population can be estimated robustly from the sample.  Moreover, even if the quantitative value depends on gene alignment parameters, its relative order is robust.  All of this work is described in our paper in BMC Genomics from 2011: Genomic fluidity: an integrative view of gene diversity within microbial populations.

However, as we were midway through our genomic fluidity paper, it occurred to us that there was one key element of this story that merited further investigation.  We had termed our metric “genomic fluidity” because it provided information on the degree to which genomes were “fluid“, i.e., comprised of different sets of genes.  The notion of fluidity also implies a dynamic, i.e., a mechanism by which genes move. Hence, I came up with a very minimal proposal for a model that could explain differences in genomic fluidity.  As it turns out, it can explain a lot more.

A null model: getting the basic concepts together
In Spring 2010, I began to explore a minimal, population-genetics style model which incorporated a key feature of genomic assays, that the gene composition of genomes differs substantially, even between taxonomically similar isolates. Hence, I thought it would be worthwhile to  analyze a model in which the total number of individuals in the population was fixed at N, and each individual had exactly M genes.  Bart and I started analyzing this together. My initial proposal was a very simple model that included three components: reproduction, mutation and gene transfer. In a reproduction step, a random individual would be selected, removed and then replaced with one of the remaining N-1 individuals.  Hence, this is exactly analogous to a Moran step in a standard neutral model.  At the time, what we termed mutation was actually representative of an uptake event, in which a random genome was selected, one of its genes was removed, and then replaced with a new gene, not found in any other of the genomes.  Finally, we considered a gene transfer step in which two genomes would be selected at random, and one gene from a given genome would be copied over to the second genome, removing one of the previous genes.  The model, with only birth-death (on left) and mutation (on right), which is what we eventually focused on for this first paper, can be depicted as follows:

We proceeded based on our physics and theoretical ecology backgrounds, by writing down master equations for genomic fluidity as a function of all three events. It is apparent that reproduction decreases genomic fluidity on average, because after a reproduction event, two genomes have exactly the same set of genes.  Likewise, gene transfer (in the original formulation) also decreases genomic fluidity on average, but the decrease is smaller by a factor of 1/M, because only one gene is transferred.  Finally, mutation increases genomic fluidity on average, because a mutation event occurring at a gene which had before occurred in more than one genome, introduces a new singleton gene in the population, hence increasing dissimilarity. The model was simple, based on physical principles, was analytically tractable, at least for average quantities like genomic fluidity, and moreover it had the right tension.  It considered a mechanism for fluidity to increase and two mechanisms for fluidity to decrease.  Hence, we thought this might provide a basis for thinking about how relative rates of birth-death, transfer and uptake might be identified from fluidity.  As it turns out, many combinations of such parameters lead to the same value of fluidity.  This is common in models, and is often referred to as an identifiability problem. However, the model could predict other things, which made it much more interesting.   


The making of the paper
The key moment when the basic model, described above, began to take shape as a paper occurred when we began to think about all the data that we were not including in our initial genomic fluidity analysis.  Most prominently, we were not considering the frequency at which genes occurred amongst different genomes.  In fact, gene frequency distributions had already attracted attention.  A gene frequency distribution summarizes the number of genes that appear in exactly k genomes. The frequency with which a gene appears is generally thought to imply something about its function, e.g., “Comprising the pan-genome are the core complement of genes common to all members of a species and a dispensable or accessory genome that is present in at leastbone but not all members of a species.” (Laing et al., BMC Bioinformatics 2011).  The emphasis is mine. But does one need to invoke selection, either implicitly or explicitly, to explain differences in gene frequency? 

As it turns out, gene frequency distributions end up having a U-shape, such that many genes appear in 1 or a few genomes, many in all genomes (or nearly all), and relatively few occur at intermediate levels.  We had extracted such gene frequency distributions from our limited dataset of ~100 genomes over 6 species.  Here is what they look like:

And, when we began to think more about our model, we realized that the tension that led to different values of genomic fluidity also generated the right sort of tension corresponding to U-shaped gene frequency distributions.  On the one-hand, mutations (e.g., uptake of new genes from the environment) would contribute to shifting the distribution to the left-hand-side of the U-shape.  On the other hand, birth-death would contribute to shifting the distribution to the right-hand side of the U-shape.  Gene transfer between genomes would also shift the distribution to the right. Hence, it seemed that for a given set of rates, it might be possible to generate reasonable fits to empirical data that would generate a U-shape. In doing so, that would mean that the U-shape was not nearly as informative as had been thought.  In fact, the U-shape could be anticipated from a neutral model in which one need not invoke selection. This is an important point as it came back to haunt us in our first round of review.

So, let me be clear: I do think that genes matter to the fitness of an organism and that if you delete/replace certain genes you will find this can have mild to severe to lethal costs (and occasional benefits).  However, our point in developing this model was to try and create a baseline null model, in the spirit of neutral theories of population genetics, that would be able to reproduce as much of the data with as few parameters as possible.  Doing so would then help identify what features of gene compositional variation could be used as a means to identify the signatures of adaptation and selection.  Perhaps this point does not even need to be stated, but obviously not everyone sees it the same way.  In fact, Eugene Koonin has made a similar argument in his nice paper, Are there laws of adaptive evolution: “the null hypothesis is that any observed pattern is first assumed to be the result of non-selective, stochastic processes, and only once this assumption is falsified, should one start to explore adaptive scenarios”.  I really like this quote, even if I don’t always follow this rule (perhaps I should). It’s just so tempting to explore adaptive scenarios first, but it doesn’t make it right.

At that point, we began extending the model in a few directions.  The major innovation was to formally map our model onto the infinitely many alleles model of population genetics, so that we could formally solve our model using the methods of coalescent theory for both cases of finite population sizes and for exponentially growing population sizes.  Bart led the charge on the analytics and here’s an example of the fits from the exponentially growing model (the x-axis is the number of genomes):

At that point, we had a model, solutions, fits to data, and a message.  We solicited a number of pre-reviews from colleagues who helped us improve the presentation (thank you for your help!).  So, we tried to publish it.    


Trying to publish the paper
We tried to publish this paper in two outlets before finding its home in BMC Genomics.  First, we submitted the article to PNAS using their new PNAS Plus format.  We submitted the paper in June 2011 and were rejected with an invitation to resubmit in July 2011. One reviewer liked the paper, apparently a lot: “I very much like the assumption of neutrality, and I think this provocative idea deserves publication.”  The same reviewer gave a number of useful and critical suggestions for improving the manuscript.  Another reviewer had a very strong negative reaction to the paper. Here was the central concern: “I feel that the authors’ conclusion that the processes shaping gene content in bacteria and primarily neutral are significantly false, and potentially confusing to readers who do not appreciate the lack of a good fit between predictions and data, and who do not realise that the U-shaped distributions observed would be expected  under models where it is selection that determines gene number.”  There was no disagreement over the method or the analysis.  The disagreement was one of what our message was.

I still am not sure how this confusion arose, because throughout our first submission and our final published version, we were clear that the point of the manuscript was to show that the U-shape of gene frequency distributions provide less information than might have been thought/expected about selection.  They are relatively easy to fit with a suite of null models.  Again, Koonin’s quote is very apt here, but at some basic level, we had an impasse over a philosophy of the type of science we were doing. Moreover, although it is clear that non-neutral processes are important, I would argue that it is also incorrect to presume that all genes are non-neutral.  There’s lots of evidence that many transferred genes have little to no effect on fitness. We revised the paper, including and solving alternative models with fixed and flexible core genomes, again showing that U-shapes are rather generic in this class of models.  We argued our point, but the editor sided with the negative review, rejecting our paper in November after resubmission in September, with the same split amongst the reviewers. 

Hence, we resubmitted the paper to Genome Biology, which rejected it at the editorial level after a few week delay without much of an explanation, and at that point, we decided to return to BMC Genomics, which we felt had been a good home for our first paper in this area and would likely make a good home for the follow-up.  A colleague once said that there should be an r-index, where r is the number of rejections a paper received before ultimate acceptance.  He argued that r-indices of 0 were likely not good (something about if you don’t fall, then you’re not trying) and an r-index of 10 was probably not good either.  I wonder what’s right or wrong. But I’ll take an r of 2 in this case, especially because I felt that the PNAS review process really helped to make the paper better even if it was ultimately rejected. And, by submitting to Genome Biology, we were able to move quickly to another journal in the same BMC consortia.

Upcoming plans
Bart Haegeman and I continue to work on this problem, from both the theory and bioinformatics side.  I find this problem incredibly fulfilling.  It turns out that there are many features of the model that we still have not fully investigated.  In addition, calculating gene frequency distributions involves a number of algorithmic challenges to scale-up to large datasets.  We are building a platform to help, to some extent, but are looking for collaborators who have specific algorithmic interests in these types of problems.  We are also in discussions with biologists who want to utilize these types of analysis to solve particular problems, e.g., how can the analysis of gene frequency distributions be made more informative with respect to understanding the role of genes in evolution and the importance of genes to fitness.  I realize there are more of such models out there tackling other problems in quantitative population genomics (we cite many of them in our BMC Genomics paper), including some in the same area of understanding the core/pan genome and gene frequency distributions. I look forward to learning from and contributing to these studies.