A Call for Change: Is Greater Transparency Necessary in Modern Day Medical Research?

“With great power comes great responsibility” - Voltaire

THIS, in just the past two weeks:

HEADLINE, JULY 30, 2014: Dutch Investigation Finds Serious Flaws In Influential New England Journal Of Medicine Study.

HEADLINE, AUGUST 5, 2014: Japanese Scientist whose stem-cell research had to be retracted when it proved to be false commits suicide. 

WHAT is happening within the world of medical research?

FOR a quick and illustrative summary of the disturbing increase in the number of retracted scientific papers, please take a moment and check out this link: http://www.nature.com/news/2011/111005/full/478026a.html

OH sure, there have always been stories about competition and rivalry amongst the scientific elite. The hallowed halls of academia are littered with them: Newton v. Hooke; Darwin v. Wallace v. The Establishment; but fabricated or intentionally skewed data? Come on now Science; we hold you to a higher degree of conduct. Heck, back in the day, a double Nobel Prize winner could receive a humiliating thrashing for rushing prematurely to publication. And why? Because despite his esteem and despite his credentials, he was wrong. And his colleagues could prove it. (Thank you very kindly Rosalind Franklin et al.) So what has changed?

OKAY so we've all been there; you know, those agonizing scarlet-faced seconds when you wish you could take back the words you've just said. But there is no taking them back. Sure, your apologies and contrite expression show you are not without manners, humility and conscience; but still, it is a difficult elephant to vanquish from the room. Now imagine that instead of seconds we are talking about months and years; and that the words coming out of your mouth are deliberate and have the potential to affect millions of lives. Lives of people who have placed their trust in the profession of which you are representative.

RECENTLY, I came across an article in The Economist telling of how attempts to reproduce results of several 'landmark' cancer studies fell far short of expectation, with a reproducibility ratio of 6 out of 53. The article goes on to suggest the need for some degree of improved transparency within the scientific community. The need for a system to be put in place which, in essence, would help keep the scientific community honest. Scientists are only human after all; and are under an enormous amount of pressure to produce and publish results; this while competing for scant funding and research grants which often come with implicit strings attached.

IN light of this disturbing trend, I could not help but be reminded of the 1998 Andrew Wakefield et al study, which through the publicity machine, came to be known as the study linking the MMR (measles, mumps & rubella) vaccine to autism. The study was originally published in The Lancet. The study was retracted in 2010.





MEASLESa

RUBELLAa

MUMPS

In its abstract, The Lancet's retraction states:

"Following the judgment of the UK General Medical Council's Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al1 are incorrect, contrary to the findings of an earlier investigation.2 In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record." 

"The British General Medical Council (GMC), which registers doctors in the United Kingdom, has decided that Dr. Andrew Wakefield should be struck from the medical register for "serious unprofessional conduct." In January 2010, the GMC Fitness to Practice Panel concluded that Wakefield had acted dishonestly and irresponsibly in connection with a research project and its subsequent publication. The fitness-to-practice hearing, which started in July 2007, centered on a study of children by Wakefield and twelve others that linked the measles-mumps-rubella (MMR) vaccine with autism and bowel problems. Subsequent studies found no connections, but sensational publicity caused immunization rates in the UK to drop more than 10%. Ten of the study's authors have since renounced its conclusions; and Lancet's editor said he should not have published the study and that Wakefield's links to litigation against the manufacturers of the MMR vaccine were a "fatal conflict of interest." 

(Above excerpt from Andrew Wakefield Loses British Medical License; by Stephen Barrett, M.D. )

I'VE read the original Wakefield et al. paper; read it again and again. And were it not for the publicity machine surrounding it, I can’t imagine it having received the mainstream attention it did. In the authors' own words: "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described." There was no conclusive evidence of any kind. Still, the authors hinted at causal links throughout, ending the discussion section with: "In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine."

The authors' choice to end the paper in that manner seemed an odd one to me, when, (granted my partiality always sways toward things genetic) this was the section which had drawn my attention:

“A genetic predisposition to autistic-spectrum disorders is suggested by over-representation in boys and a greater concordance rate in monozygotic than in dizygotic twins.15 In the context of susceptibility to infection, a genetic association with autism, linked to a null allele of the complement (C) 4B gene located in the class III region of the major-histocompatibility complex, has been recorded by Warren and colleagues.24 C4B-gene products are crucial for the activation of the complement pathway and protection against infection: individuals inheriting one or two C4B null alleles may not handle certain viruses appropriately, possibly including attenuated strains.”

WHY did this draw my attention?

Since genetics were acknowledged as a potential contributing factor, it seemed deserving of at least an equal amount attention as the MMR vaccine itself.

WHY?

Well, because perhaps if back in 1998 such an association had been given more than an honourable mention, the option of genetic screening prior to vaccination could have by this time become an acceptable alternative to outright refusal. (And yes, I do realize I'm speaking in hypotheticals; and yes, the genetic component was just one of several noted, but that is exactly my point: whatever the authors' intent, their actions and subsequent actions may have caused the forest to be obscured by the trees.)

IN case anyone is wondering, yes I did do a Google search for ‘scholarly articles supporting link between MMR and autism;’ and I'm not saying they don't exist, just that my efforts returned a whole lot of this:

THAT said, here are a few links from the 'other side' of the vaccine story:

http://www.collective-evolution.com/2013/05/08/italian-court-rules-mmr-vaccine-caused-autism-us-media-blacks-out-story/

http://articles.mercola.com/sites/articles/archive/2011/02/07/new-research-shows-link-between-mmr-vaccine-and-autism.aspx
http://www.ageofautism.com/dr-andrew-wakefield/
http://vactruth.com/tag/dr-andrew-wakefield/

AS WELL, www.thelibertybeacon.com, provides a list of "28 studies from around the world that support Dr. Wakefield's research." (Scroll to the bottom of the web page for the list.) And yup, I did read them; read them all; read them 'till my eyes went dry. Yup, yup, yup ... But the truth is, I'm still not seeing it ... Okay, so they did say 'support' not 'prove'; and 'support' can be interpreted in many ways, right? Well, as I prefer to reserve my proselytizing for topics upon which I have a concrete stance, (like my aversion to altered data, skewed facts and biased interpretations in scientific papers) perhaps it is best if I invite you to read the studies for yourselves. After all, we, each of us, have our own unique set of criteria upon which our opinions are formed.

IT IS estimated that nearly two million scientific papers are published each year, with only a relative handful ever reaching the mainstream. The original Wakefield et al paper should never have reached the mainstream. The study lacked controls, full stop. And it is impossible for the interpretation of data from any scientific study, conducted in the absence of controls to render any definitive conclusions. And yet it has reached the mainstream, and now we find ourselves engaged in a dangerous standoff of my science trumps your science.

It is a very human need indeed, the need to know why. It is essential to our survival and often driven by how directly the answers sought affect us personally. And it is a question which remains at the heart of the scientific endeavor. We place our confidence and trust in scientists, and with good reason. But in order to maintain that trust, perhaps it has become necessary to open the window, even just a sliver, as this would go a long way toward ebbing the tide of falsified, biased and redundant research. Falsified, biased and redundant research which, when seeped into the mainstream, has consequences which no amount of retracting can undo. With lives on the line, the current trend cannot continue. Immediate changes need to be implemented in order to protect the interests of both the researchers and those who rely on the important work they do.

UPDATES / RELATED

sciencemag.org / Feature: Cancer reproducibility effort faces backlash / June 25, 2015

howstuffworks.com  June 19, 2015  Fraudulent Findings and Laboratory Lies: The Science Scandals Quiz

livescience.com Jan. 29, 2015 Spike in Measles Cases Due to People Skipping Vaccinations

Science News Jan. 13, 2015 Is Redoing Scientific Research the Best Way to Find Truth

SOURCES

http://cid.oxfordjournals.org/content/48/4/456.full
http://vactruth.com/tag/dr-andrew-wakefield/
http://www.thelibertybeacon.com/2013/06/21/new-published-study-verifies-andrew-wakefields-research-on-autism-again-mmr-vaccine-causes-autism/ 
http://www.ageofautism.com/dr-andrew-wakefield/
http://www.measlesrubellainitiative.org/measles-outbreaks-mid-year-2013-update/
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(08)70282-2/fulltext
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)11096-0/fulltext
http://scienceblogs.com/insolence/2007/01/01/surprise-surprise-andrew-wakefield-was-p/
http://www.economist.com/news/leaders/21588069-scientific-research-has-changed-world-now-it-needs-change-itself-how-science-goes-wrong
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)11096-0/fulltext
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60175-4/fulltext
http://www.dailymail.co.uk/news/article-2716540/Japanese-scientist-stem-cell-research-retracted-proved-false-commits-suicide.html
http://www.forbes.com/sites/larryhusten/2014/07/30/dutch-investigation-finds-serious-flaws-in-influential-new-england-journal-of-medicine-study/
http://www.salon.com/2014/07/22/vaccine_truthers_arent_alone_nearly_half_of_americans_believe_medical_conspiracy_theories/?utm_source=facebook&utm_medium=socialflow
http://www.health.gov.on.ca/en/public/programs/immunization/#.U0v0B_EAmKM.facebook
http://www.forbes.com/sites/emilywillingham/2014/03/23/worried-about-measles-dont-call-dr-bob-sears/
http://www.theguardian.com/commentisfree/2014/aug/08/science-research-grants-awarded-on-the-basis-of-patents-is-patently-wrong
http://www.sciencebasedmedicine.org/wakefield-fights-back/
http://briandeer.com/wakefield-deer.htm
http://articles.mercola.com/sites/articles/archive/2011/02/07/new-research-shows-link-between-mmr-vaccine-and-autism.aspx
http://www.collective-evolution.com/2013/05/08/italian-court-rules-mmr-vaccine-caused-autism-us-media-blacks-out-story/
http://retractionwatch.com/
http://www.nature.com/news/2011/111005/full/478026a.html
http://www.ncbi.nlm.nih.gov/pubmed/20452682
http://www.smithsonianmag.com/ist/?next=/smart-news/half-academic-studies-are-never-read-more-three-people-180950222/

  

IMAGE CREDITS

"Mumps PHIL 130 lores" by Photo Credit:Content Providers: CDC/NIP/Barbara Rice - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #130.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Mumps_PHIL_130_lores.jpg#mediaviewer/File:Mumps_PHIL_130_lores.jpg

"RougeoleDP" by CDC/NIP/Barbara Rice - http://phil.cdc.gov/phil/ (ID#: 132). Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:RougeoleDP.jpg#mediaviewer/File:RougeoleDP.jpg

"Rash of rubella on skin of child's back" by http://phil.cdc.gov/PHIL_Images/03052002/00002/PHIL_712_lores.jpg. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Rash_of_rubella_on_skin_of_child%27s_back.JPG#mediaviewer/File:Rash_of_rubella_on_skin_of_child%27s_back.JPG

Our Common Foe

Viruses

 Unable to replicate in the absence of a host cell, viruses are essentially parasitic nucleic acids, naked, except for an outer protein loincloth to shield their modesty. Fortunately for them, they are adept at commandeering the cellular machinery of host cells for their own ends.

In the absence of fossil records, it is difficult to estimate their age. Are modern day viruses the descendants of earth’s earliest life-forms, or some evolutionary remnant? Bacteria date back to at least 3.5 billion years. And the host specific targeting of bacteria by phages could suggest some form of co-evolution. 



bacteriophages attached to a
bacterial cell wall

Once inside the host cell they can replicate like viral rabbits, causing the host cell to rupture and release their viral progeny in search of more host cells. And, or, they can incorporate their genetic material into the host genome and lay dormant until some stress factor induces replication.

Viruses can be our allies in research and in combating harmful bacteria, (as is the case with the aforementioned bacteriophage) or our worst enemies.

Our current defense strategies include: evasive measures (hygiene, sanitation, quarantine and education) natural or acquired immunity (in utero, vaccines) as well as post-infection treatments like  mono-clonal antibodies and antiretroviral drugs (ARV's interfere with viral replication in host cell.)

And these measures can and do save millions of lives.

That more than 55,000 people still die each year from rabies is a tragic statistic. Still, the fact that each year more than 15 million people receive the post-exposure rabies vaccine, thus preventing the death toll from climbing higher is cause for measured optimism.
That cholera still takes the lives of 100,000-120,000 people each year is beyond tragic. But what would that figure look like in the absence of public health, education, access to rehydration salts and improved sanitation?

 *



Increase over time in the cases and deaths during
the 2014 outbreak

In a perfect world, we would not view human suffering through the detached lens of 'us' and 'them.' In a perfect world, we would not require a critical tipping point to be reached before affordable medicines and diagnostics became available to a market dearly in need. In a perfect world, political, governmental, societal, religious, financial and geographical barriers would not exist to impede the ability of help to reach those in need. 

One of the many questions that came to my mind in reading about the recent outbreak of Ebola in West Africa was the hypothetical: If a vaccine were to become available tomorrow, would it have the power to end this crisis? Case in point, Polio, a disease nearly eradicated, which has been steadily rearing its viral head in at least three countries, "with 99 cases reported so far this year in Pakistan."

For the administration of any treatment to be effective, it must work in concert with the implementation of focused strategies by Government Ministries. Strategies encompassing the coordination of efforts at both the national and international level, accessibility, education, and improvements in agricultural practices, sanitation and public health.

*

 During the 2003 SARS outbreak, my job took me into hospitals on a daily basis; where, upon my entry I was questioned, masked, gloved and had my temperature taken. It never occurred to me not to proceed. I didn't feel fear. I felt protected, even a little annoyed by the precautions being enforced by the invisible hand.* Despite my mild annoyance, I trusted the hand to keep me safe; I trusted that in enforcing such measures, it had the best interest of the population in mind. I have never known the fear of diseases against which vaccinations exist, nor those treatable by antibiotics. That is not to say that apprehensions do not linger on the periphery, rather, that I do not feel them acutely. They don't affect my daily life. To a large extent, I feel there is a safety net below me. Speaking for myself, from my Canadian perspective, I feel very fortunate indeed to have such infrastructures in place; but what about the countries, cities, towns and villages where such infrastructures do not exist? It goes without saying that we should feel empathic and compelled to assist in whatever manner we are capable. But even for those who view the world as 'us' and 'them' and 'not my problem,' this question of infrastructure is one to be considered very carefully. We live in a time and on a planet where there are few limitations on the transit routes of potential pathogenic hosts. We are after all, as one as a species on this giant blue orb and pathogens have no respect for geographic borders. *(Not intended to be a reference to Adam Smith)



  

EBOLA








We know how to prevent the transmission of Ebola. And with proper measures in place its spread can be effectively contained. Ebola is not (yet) air-borne. And at present, if detected in the early stages, the likelihood of surviving the infection is improving. So why is this most recent Ebola outbreak terrorizing West Africa and threatening to spread across borders?

The answers to that question are provided in a clear and concise manner in this link to the August 1, 2014 WHO Director-General's 'Overview of the Ebola situation delivered to the Presidents of Guinea, Liberia, and Sierra Leone.'

Below are a few excerpts taken from the address made by Dr. Margaret Chan, Director-General of the World Health Organization.

"West Africa’s outbreak is caused by the most lethal strain in the family of Ebola viruses.
... It is the largest in terms of numbers of cases and deaths, with 1,323 cases and 729 deaths reported to date in four countries.
It is the largest in terms of geographical areas already affected and others at immediate risk of further spread.
... It is taking place in areas with fluid population movements over porous borders, and it has demonstrated its ability to spread via air travel, contrary to what has been seen in past outbreaks.
...this outbreak is moving faster than our efforts to control it. If the situation continues to deteriorate, the consequences can be catastrophic in terms of lost lives but also severe socioeconomic disruption and a high risk of spread to other countries.
... This is not an airborne virus. Transmission requires close contact with the bodily fluids of an infected person, also after death. Apart from this specific situation, the general public is not at high risk of infection by the Ebola virus. At the same time, it would be extremely unwise for national authorities and the international community to allow an Ebola virus to circulate widely and over a long period of time in human populations. Constant mutation and adaptation are the survival mechanisms of viruses and other microbes.
... We must not give this virus opportunities to deliver more surprises."










There are certain situations in which I don't believe intent matters; that is to say, if we wait around for pure intentions, we may never accomplish much of anything. So if the intent behind our decision to help combat the spread of this disease; to assist financially, medically, pharmaceutically and/or logistically, is based upon our concerns about Ebola spreading across oceans, then so-be-it; that's okay. Whatever the motivation, when we consider the current lack of containment, the variable incubation period (anywhere from 2-21 days,) the absence of licensed vaccine and the lethality of this virus, it is clear that the need for efforts to be escalated (in a coordinated manner) is most urgent indeed.

Science fiction may conjure fears of an imminent alien threat. Wars may rage on and 


 Influenza genetic shift

on with battle lines drawn in shifting sands, and with lives lost to shrapnel and bullets and blast. But there is a common threat that connects each member of the human race, and it is indifferent to our beliefs, prejudice, geography, skin colour, sex, commerce and religion. Namely, the threat we face from the pathogenic foes against whom we are incalculably outnumbered. Their stealth and streamlined simplicity allows for rapid infiltration, replication and adaptability.Locked in an arms race, our ability to stay one step ahead is largely dependent upon the singularly human arsenal of intelligence, compassion and shared experience. All three are equally important for the survival of our species, for though it may provide the premise for an entertaining film, I would not want to live in any version of the dystopia created should factors converge which would enable this foe (or any of its relations) to gain the upper hand.

UPDATES:

http://www.dailymail.co.uk/news/article-2746200/Sierra-Leone-placed-lockdown-residents-told-stay-inside-homes-three-days-effort-stop-spread-Ebola.html

http://www.huffingtonpost.ca/2014/08/28/first-human-study-of-cana_n_5733236.html

http://www.buzzfeed.com/jinamoore/two-days-after-it-opens-mob-destroys-ebola-center-in-liberia#20uwjlq

http://www.voanews.com/content/nigeria-confirms-ebola-cases-from-secondary-contact-with-victims/2424563.html






SOURCES

http://www.vox.com/2014/7/31/5952515/facts-you-should-know-about-the-ebola-outbreak?utm_medium=social&utm_source=twitter&utm_campaign=voxdotcom&utm_content=thursday
http://www.who.int/dg/speeches/2014/ebola/en/
http://www.buzzfeed.com/jimdalrympleii/this-is-how-ebola-compares-to-other-recent-big-epidemics
http://time.com/3051398/polio-pakistan-rotary/
http://www.who.int/mediacentre/factsheets/fs107/en/
http://www.who.int/mediacentre/factsheets/fs099/en/
http://www.astrobio.net/topic/origins/extreme-life/tracking-viruses-back-in-time/
http://www.who.int/mediacentre/factsheets/fs103/en/
https://testtube.com/dnews/can-you-recover-from-ebola/
http://www.forbes.com/sites/davidkroll/2014/08/05/ebola-secret-serum-small-biopharma-the-army-and-big-tobacco/
http://www.who.int/hiv/topics/treatment/en/
http://en.wikipedia.org/wiki/Virus
http://en.wikipedia.org/wiki/Ebola_virus_disease


IMAGE CREDITS

"Phage" by Dr Graham Beards - en:Image:Phage.jpg. Licensed under Public domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Phage.jpg#mediaviewer/File:Phage.jpg

"Diseased Ebola 2014" by Leopoldo Martin R - Own work. Licensed under Creative Commons Attribution-Share Alike 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Diseased_Ebola_2014.png#mediaviewer/File:Diseased_Ebola_2014.png 

"Ebola virus virion" by CDC/Cynthia Goldsmith - Public Health Image Library, #10816This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #10816.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−. Licensed under Public domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Ebola_virus_virion.jpg#mediaviewer/File:Ebola_virus_virion.jpg

"EbolaCycle" by CDC - http://www.cdc.gov/vhf/ebola/resources/virus-ecology.html. Licensed under Public domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:EbolaCycle.png#mediaviewer/File:EbolaCycle.png

"Symptoms of ebola" by Mikael Häggström - Own work. Source information:Ebola Hemorrhagic Fever from Centers for Disease Control and Prevention.P age last updated: January 28, 2014.. Licensed under Creative Commons Zero, Public Domain Dedication via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Symptoms_of_ebola.png#mediaviewer/File:Symptoms_of_ebola.png

 "Influenza geneticshift" by Influenza_geneticshift.jpg: Dhorspool at en.wikipediaderivative work: Jiver - This file was derived from:Influenza_geneticshift.jpg. Licensed under Creative Commons Attribution-Share Alike 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Influenza_geneticshift.svg#mediaviewer/File:Influenza_geneticshift.svg