The Road to Bad Science Is Paved with Obedience and Secrecy

We often laud intellectual diversity of a scientific research group because we hope that the multitude of opinions can help point out flaws and improve the quality of research long before it is finalized and written up as a manuscript. The recent events surrounding the research in one of the world's most famous stem cell research laboratories at Harvard shows us the disastrous effects of suppressing diverse and dissenting opinions.
The infamous "Orlic paper" was a landmark research article published in the prestigious scientific journal Nature in 2001, which showed that stem cells contained in the bone marrow could be converted into functional heart cells. After a heart attack, injections of bone marrow cells reversed much of the heart attack damage by creating new heart cells and restoring heart function. It was called the "Orlic paper" because the first author of the paper was Donald Orlic, but the lead investigator of the study was Piero Anversa, a professor and highly respected scientist at New York Medical College.

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Anversa had established himself as one of the world's leading experts on the survival and death of heart muscle cells in the 1980s and 1990s, but with the start of the new millennium, Anversa shifted his laboratory's focus towards the emerging field of stem cell biology and its role in cardiovascular regeneration. The Orlic paper was just one of several highly influential stem cell papers to come out of Anversa's lab at the onset of the new millenium. A 2002 Anversa paper in the New England Journal of Medicine – the world's most highly cited academic journal –investigated the hearts of human organ transplant recipients. This study showed that up to 10% of the cells in the transplanted heart were derived from the recipient's own body. The only conceivable explanation was that after a patient received another person's heart, the recipient's own cells began maintaining the health of the transplanted organ. The Orlic paper had shown the regenerative power of bone marrow cells in mouse hearts, but this new paper now offered the more tantalizing suggestion that even human hearts could be regenerated by circulating stem cells in their blood stream.


A 2003 publication in Cell by the Anversa group described another ground-breaking discovery, identifying a reservoir of stem cells contained within the heart itself. This latest coup de force found that the newly uncovered heart stem cell population resembled the bone marrow stem cells because both groups of cells bore the same stem cell protein called c-kit and both were able to make new heart muscle cells. According to Anversa, c-kit cells extracted from a heart could be re-injected back into a heart after a heart attack and regenerate more than half of the damaged heart!

These Anversa papers revolutionized cardiovascular research. Prior to 2001, most cardiovascular researchers believed that the cell turnover in the adult mammalian heart was minimal because soon after birth, heart cells stopped dividing. Some organs or tissues such as the skin contained stem cells which could divide and continuously give rise to new cells as needed. When skin is scraped during a fall from a bike, it only takes a few days for new skin cells to coat the area of injury and heal the wound. Unfortunately, the heart was not one of those self-regenerating organs. The number of heart cells was thought to be more or less fixed in adults. If heart cells were damaged by a heart attack, then the affected area was replaced by rigid scar tissue, not new heart muscle cells. If the area of damage was large, then the heart's pump function was severely compromised and patients developed the chronic and ultimately fatal disease known as "heart failure".

Anversa's work challenged this dogma by putting forward a bold new theory: the adult heart was highly regenerative, its regeneration was driven by c-kit stem cells, which could be isolated and used to treat injured hearts. All one had to do was harness the regenerative potential of c-kit cells in the bone marrow and the heart, and millions of patients all over the world suffering from heart failure might be cured. Not only did Anversa publish a slew of supportive papers in highly prestigious scientific journals to challenge the dogma of the quiescent heart, he also happened to publish them at a unique time in history which maximized their impact.

In the year 2001, there were few innovative treatments available to treat patients with heart failure. The standard approach was to use medications that would delay the progression of heart failure. But even the best medications could not prevent the gradual decline of heart function. Organ transplants were a cure, but transplantable hearts were rare and only a small fraction of heart failure patients would be fortunate enough to receive a new heart. Hopes for a definitive heart failure cure were buoyed when researchers isolated human embryonic stem cells in 1998. This discovery paved the way for using highly pliable embryonic stem cells to create new heart muscle cells, which might one day be used to restore the heart's pump function without  resorting to a heart transplant.

The dreams of using embryonic stem cells to regenerate human hearts were soon squashed when the Bush administration banned the generation of new human embryonic stem cells in 2001, citing ethical concerns. These federal regulations and the lobbying of religious and political groups against human embryonic stem cells were a major blow to research on cardiovascular regeneration. Amidst this looming hiatus in cardiovascular regeneration, Anversa's papers appeared and showed that one could steer clear of the ethical controversies surrounding embryonic stem cells by using an adult patient's own stem cells. The Anversa group re-energized the field of cardiovascular stem cell research and cleared the path for the first human stem cell treatments in heart disease.

Instead of having to wait for the US government to reverse its restrictive policy on human embryonic stem cells, one could now initiate clinical trials with adult stem cells, treating heart attack patients with their own cells and without having to worry about an ethical quagmire. Heart failure might soon become a disease of the past. The excitement at all major national and international cardiovascular conferences was palpable whenever the Anversa group, their collaborators or other scientists working on bone marrow and cardiac stem cells presented their dizzyingly successful results. Anversa received numerous accolades for his discoveries and research grants from the NIH (National Institutes of Health) to further develop his research program. He was so successful that some researchers believed Anversa might receive the Nobel Prize for his iconoclastic work which had redefined the regenerative potential of the heart. Many of the world's top universities were vying to recruit Anversa and his group, and he decided to relocate his research group to Harvard Medical School and Brigham and Women's Hospital 2008.

There were naysayers and skeptics who had resisted the adult stem cell euphoria. Some researchers had spent decades studying the heart and found little to no evidence for regeneration in the adult heart. They were having difficulties reconciling their own results with those of the Anversa group. A number of practicing cardiologists who treated heart failure patients were also skeptical because they did not see the near-miraculous regenerative power of the heart in their patients. One Anversa paper went as far as suggesting that the whole heart would completely regenerate itself roughly every 8-9 years, a claim that was at odds with the clinical experience of practicing cardiologists.  Other researchers pointed out serious flaws in the Anversa papers. For example, the 2002 paper on stem cells in human heart transplant patients claimed that the hearts were coated with the recipient's regenerative cells, including cells which contained the stem cell marker Sca-1. Within days of the paper's publication, many researchers were puzzled by this finding because Sca-1 was a marker of mouse and rat cells – not human cells! If Anversa's group was finding rat or mouse proteins in human hearts, it was most likely due to an artifact. And if they had mistakenly found rodent cells in human hearts, so these critics surmised, perhaps other aspects of Anversa's research were similarly flawed or riddled with artifacts.

At national and international meetings, one could observe heated debates between members of the Anversa camp and their critics. The critics then decided to change their tactics. Instead of just debating Anversa and commenting about errors in the Anversa papers, they invested substantial funds and efforts to replicate Anversa's findings. One of the most important and rigorous attempts to assess the validity of the Orlic paper was published in 2004, by the research teams of Chuck Murry and Loren Field. Murry and Field found no evidence of bone marrow cells converting into heart muscle cells. This was a major scientific blow to the burgeoning adult stem cell movement, but even this paper could not deter the bone marrow cell champions.

Despite the fact that the refutation of the Orlic paper was published in 2004, the Orlic paper continues to carry the dubious distinction of being one of the most cited papers in the history of stem cell research. At first, Anversa and his colleagues would shrug off their critics' findings or publish refutations of refutations – but over time, an increasing number of research groups all over the world began to realize that many of the central tenets of Anversa's work could not be replicated and the number of critics and skeptics increased. As the signs of irreplicability and other concerns about Anversa's work mounted, Harvard and Brigham and Women's Hospital were forced to initiate an internal investigation which resulted in the retraction of one Anversa paper and an expression of concern about another major paper. Finally, a research group published a paper in May 2014 using mice in which c-kit cells were genetically labeled so that one could track their fate and found that c-kit cells have a minimal – if any – contribution to the formation of new heart cells: a fraction of a percent!

The skeptics who had doubted Anversa's claims all along may now feel vindicated, but this is not the time to gloat. Instead, the discipline of cardiovascular stem cell biology is now undergoing a process of soul-searching. How was it possible that some of the most widely read and cited papers were based on heavily flawed observations and assumptions? Why did it take more than a decade since the first refutation was published in 2004 for scientists to finally accept that the near-magical regenerative power of the heart turned out to be a pipe dream.

One reason for this lag time is pretty straightforward: It takes a tremendous amount of time to refute papers. Funding to conduct the experiments is difficult to obtain because grant funding agencies are not easily convinced to invest in studies replicating existing research. For a refutation to be accepted by the scientific community, it has to be at least as rigorous as the original, but in practice, refutations are subject to even greater scrutiny. Scientists trying to disprove another group's claim may be asked to develop even better research tools and technologies so that their results can be seen as more definitive than those of the original group. Instead of relying on antibodies to identify c-kit cells, the 2014 refutation developed a transgenic mouse in which all c-kit cells could be genetically traced to yield more definitive results - but developing new models and tools can take years.

The scientific peer review process by external researchers is a central pillar of the quality control process in modern scientific research, but one has to be cognizant of its limitations. Peer review of a scientific manuscript is routinely performed by experts for all the major academic journals which publish original scientific results. However, peer review only involves a "review", i.e. a general evaluation of major strengths and flaws, and peer reviewers do not see the original raw data nor are they provided with the resources to replicate the studies and confirm the veracity of the submitted results. Peer reviewers rely on the honor system, assuming that the scientists are submitting accurate representations of their data and that the data has been thoroughly scrutinized and critiqued by all the involved researchers before it is even submitted to a journal for publication. If peer reviewers were asked to actually wade through all the original data generated by the scientists and even perform confirmatory studies, then the peer review of every single manuscript could take years and one would have to find the money to pay for the replication or confirmation experiments conducted by peer reviewers. Publication of experiments would come to a grinding halt because thousands of manuscripts would be stuck in the purgatory of peer review. Relying on the integrity of the scientists submitting the data and their internal review processes may seem naïve, but it has always been the bedrock of scientific peer review. And it is precisely the internal review process which may have gone awry in the Anversa group.

Pygmalion and Glatea by Louis Gauffier (via Wikimedia - Public Domain)

Just like Pygmalion fell in love with Galatea, researchers fall in love with the hypotheses and theories that they have constructed. To minimize the effects of these personal biases, scientists regularly present their results to colleagues within their own groups at internal lab meetings and seminars or at external institutions and conferences long before they submit their data to a peer-reviewed journal. The preliminary presentations are intended to spark discussions, inviting the audience to challenge the veracity of the hypotheses and the data while the work is still in progress. Sometimes fellow group members are truly skeptical of the results, at other times they take on the devil's advocate role to see if they can find holes in their group's own research. The larger a group, the greater the chance that one will find colleagues within a group with dissenting views. This type of feedback is a necessary internal review process which provides valuable insights that can steer the direction of the research.
Considering the size of the Anversa group – consisting of 20, 30 or even more PhD students, postdoctoral fellows and senior scientists – it is puzzling why the discussions among the group members did not already internally challenge their hypotheses and findings, especially in light of the fact that they knew extramural scientists were having difficulties replicating the work.
Retraction Watch is one of the most widely read scientific watchdogs which tracks scientific misconduct and retractions of published scientific papers. Recently, Retraction Watch published the account of an anonymous whistleblower who had worked as a research fellow in Anversa's group and provided some unprecedented insights into the inner workings of the group, which explain why the internal review process had failed:

"I think that most scientists, perhaps with the exception of the most lucky or most dishonest, have personal experience with failure in science—experiments that are unreproducible, hypotheses that are fundamentally incorrect. Generally, we sigh, we alter hypotheses, we develop new methods, we move on. It is the data that should guide the science.
 In the Anversa group, a model with much less intellectual flexibility was applied. The "Hypothesis" was that c-kit (cd117) positive cells in the heart (or bone marrow if you read their earlier studies) were cardiac progenitors that could: 1) repair a scarred heart post-myocardial infarction, and: 2) supply the cells necessary for cardiomyocyte turnover in the normal heart.
 This central theme was that which supplied the lab with upwards of $50 million worth of public funding over a decade, a number which would be much higher if one considers collaborating labs that worked on related subjects.
 In theory, this hypothesis would be elegant in its simplicity and amenable to testing in current model systems. In practice, all data that did not point to the "truth" of the hypothesis were considered wrong, and experiments which would definitively show if this hypothesis was incorrect were never performed (lineage tracing e.g.)."

Discarding data that might have challenged the central hypothesis appears to have been a central principle.


According to the whistleblower, Anversa's group did not just discard undesirable data, they actually punished group members who would question the group's hypotheses:

"In essence, to Dr. Anversa all investigators who questioned the hypothesis were "morons," a word he used frequently at lab meetings. For one within the group to dare question the central hypothesis, or the methods used to support it, was a quick ticket to dismissal from your position."

The group also created an environment of strict information hierarchy and secrecy which is antithetical to the spirit of science:

"The day to day operation of the lab was conducted under a severe information embargo. The lab had Piero Anversa at the head with group leaders Annarosa Leri, Jan Kajstura and Marcello Rota immediately supervising experimentation. Below that was a group of around 25 instructors, research fellows, graduate students and technicians. Information flowed one way, which was up, and conversation between working groups was generally discouraged and often forbidden.
 Raw data left one's hands, went to the immediate superior (one of the three named above) and the next time it was seen would be in a manuscript or grant. What happened to that data in the intervening period is unclear.
 A side effect of this information embargo was the limitation of the average worker to determine what was really going on in a research project. It would also effectively limit the ability of an average worker to make allegations regarding specific data/experiments, a requirement for a formal investigation."

This segregation of information is a powerful method to maintain an authoritarian rule and is more typical for terrorist cells or intelligence agencies than for a scientific lab, but it would definitely explain how the Anversa group was able to mass produce numerous irreproducible papers without any major dissent from within the group.
In addition to the secrecy and segregation of information, the group also created an atmosphere of fear to ensure obedience:

"Although individually-tailored stated and unstated threats were present for lab members, the plight of many of us who were international fellows was especially harrowing. Many were technically and educationally underqualified compared to what might be considered average research fellows in the United States. Many also originated in Italy where Dr. Anversa continues to wield considerable influence over biomedical research.
 This combination of being undesirable to many other labs should they leave their position due to lack of experience/training, dependent upon employment for U.S. visa status, and under constant threat of career suicide in your home country should you leave, was enough to make many people play along.
 Even so, I witnessed several people question the findings during their time in the lab. These people and working groups were subsequently fired or resigned. I would like to note that this lab is not unique in this type of exploitative practice, but that does not make it ethically sound and certainly does not create an environment for creative, collaborative, or honest science."

Foreign researchers are particularly dependent on their employment to maintain their visa status and the prospect of being fired from one's job can be terrifying for anyone.
This is an anonymous account of a whistleblower and as such, it is problematic. The use of anonymous sources in science journalism could open the doors for all sorts of unfounded and malicious accusations, which is why the ethics of using anonymous sources was heavily debated at the recent ScienceOnline conference. But the claims of the whistleblower are not made in a vacuum – they have to be evaluated in the context of known facts. The whistleblower's claim that the Anversa group and their collaborators received more than $50 million to study bone marrow cell and c-kit cell regeneration of the heart can be easily verified at the public NIH grant funding RePORTer website. The whistleblower's claim that many of the Anversa group's findings could not be replicated is also a verifiable fact. It may seem unfair to condemn Anversa and his group for creating an atmosphere of secrecy and obedience which undermined the scientific enterprise, caused torment among trainees and wasted millions of dollars of tax payer money simply based on one whistleblower's account. However, if one looks at the entire picture of the amazing rise and decline of the Anversa group's foray into cardiac regeneration, then the whistleblower's description of the atmosphere of secrecy and hierarchy seems very plausible.

The investigation of Harvard into the Anversa group is not open to the public and therefore it is difficult to know whether the university is primarily investigating scientific errors or whether it is also looking into such claims of egregious scientific misconduct and abuse of scientific trainees. It is unlikely that Anversa's group is the only group that might have engaged in such forms of misconduct. Threatening dissenting junior researchers with a loss of employment or visa status may be far more common than we think. The gravity of the problem requires that the NIH – the major funding agency for biomedical research in the US – should look into the prevalence of such practices in research labs and develop safeguards to prevent the abuse of science and scientists.

New White House Budget: NIH funding will not be restored to pre-sequester levels

The Federation of American Societies for Experimental Biology (FASEB) recommended that the White House increase the annual NIH budget to $32 billion dollars to help restore US biomedical research funding levels to those of 2003 (link):

The broad program of research supported by NIH is essential for advancing our understanding of basic biological functions, reducing human suffering, and protecting the country against new and re-emerging disease threats. Biomedical research is also a primary source of new innovations in health care and other areas.  

Exciting new NIH initiatives are poised to accelerate our progress in the search for cures. It would be tragic if we could not capitalize on the many opportunities before us. The development of a universal vaccine to protect adults and children against both seasonal and pandemic flu and development of gene chips and DNA sequencing technologies that can predict risk for high blood pressure, kidney disease, diabetes, and obesity are just a few of the research breakthroughs that will be delayed if we fail to sustain the investment in NIH.  

As a result of our prior investment, we are the world leader in biomedical research. We should not abdicate our competitive edge. Without adequate funding, NIH will have to sacrifice valuable lines of research. The termination of ongoing studies and the diminished availability of grant support will result in the closure of laboratories and the loss of highly skilled jobs. At a time when we are trying to encourage more students to pursue science and engineering studies, talented young scientists are being driven from science by the disruption of their training and lack of career opportunities.

Rising costs of research, the increasing complexity of the scientific enterprise, and a loss of purchasing power at NIH due to flat budgets have made it increasingly competitive for individual investigators to obtain funding. Today, only one in six grant applications will be supported, the lowest rate in NIH history. Increasing the NIH budget to $32.0 billion would provide the agency with an additional $1.36 billion which could restore funding for R01 grants (multiyear awards to investigators for specified projects) back to the level achieved in 2003 and support an additional 1,700 researchers while still providing much needed financial support for other critical areas of the NIH portfolio.

Unfortunately, the released White House budget (PDF) will only provide a minimal increase in annual NIH funding from $29.9 billion to $ 30.2 billion, which is still lower than the pre-sequester $30.6 billion.

It is much lower than what FASEB had suggested and it is going to be increasingly difficult for US biomedical research to sustain its competitive edge. The White House budget also emphasizes neuroscience and Alzheimer's research:

Biomedical research contributes to improving the health of the American people. The Budget includes $30.2 billion for NIH to support research at institutions across the United States, continuing the Administration’s commitment to investment in Alzheimer’s research and NIH’s contribution to the multiagency BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative. The Budget increases funding for innovative, high-risk high-reward research to help spur development of new therapeutics to treat diseases and disorders that affect millions of Americans, such as cancer and Alzheimer’s disease. The Budget includes funding for a new advanced research program modeled after the cutting-edge Defense Advanced Research Projects Agency (DARPA) program at the Department of Defense. NIH will also implement new policies to improve transparency and reduce administrative costs. The Opportunity, Growth, and Security Initiative includes an additional $970 million for NIH, which would support about 650 additional new grants and further increase funding for the BRAIN and DARPA-inspired initiatives, and invest in other critical priorities.    

While this is good news for neuroscientists, the essentially flat NIH budget will force the NIH to cut funding to basic biomedical research in non-neuroscience areas including basic cell biology, molecular biology and biochemistry.

The outlook for US biomedical research remains gloomy.

The Science Mystique

Many of my German high school teachers were intellectual remnants of the “68er” movement. They had either been part of the 1968 anti-authoritarian and left-wing student protests in Germany or they had been deeply influenced by them. The movement gradually fizzled out and the students took on seemingly bourgeois jobs in the 1970s as civil servants, bank accountants or high school teachers, but their muted revolutionary spirit remained on the whole intact. Some high school teachers used the flexibility of the German high school curriculum to infuse us with the revolutionary ideals of the 68ers. For example, instead of delving into Charles Dickens in our English classes, we read excerpts of the book “The Feminine Mystique” written by the American feminist Betty Friedan.

Our high school level discussion of the book barely scratched the surface of the complex issues related to women’s rights and their portrayal by the media, but it introduced me to the concept of a “mystique”. The book pointed out that seemingly positive labels such as “nurturing” were being used to propagate an image of the ideal woman, who could fulfill her life’s goals by being a subservient and loving housewife or mother. She might have superior managerial skills, but they were best suited to run a household and not a company, and she would need to be protected from the aggressive male-dominated business world. Many women bought into this mystique, precisely because it had elements of praise built into it, without realizing how limiting it was to be placed on a pedestal. Even though the feminine mystique has largely been eroded in Europe and North America, I continue to encounter women who cling on to this mystique, particularly among Muslim women in North America who are prone to emphasize how they feel that gender segregation and restrictive dress codes for women are a form of “elevation” and honor. They claim these social and personal barriers make them feel unique and precious.

Friedan’s book also made me realize that we were surrounded by so many other similarly captivating mystiques. The oriental mystique was dismantled by Edward Said in his book “Orientalism”, and I have to admit that I myself was transiently trapped in this mystique. Being one of the few visibly “oriental” individuals among my peers in Germany, I liked the idea of being viewed as exotic, intuitive and emotional. After I started medical school, I learned about the “doctor mystique”, which was already on its deathbed. Doctors had previously been seen as infallible saviors who devoted all their time to heroically saving lives and whose actions did not need to be questioned. There is a German expression for doctors which is nowadays predominantly used in an ironic sense: “Halbgötter in Weiß” – Demigods in White. Through persistent education, books, magazine and newspaper articles, TV shows and movies, many of these mystiques have been gradually demolished.

It has become common knowledge that women can be successful as ambitious CEOs or as brilliant engineers. We now know that “Orientals” do not just indulge their intuitive mysticism but can become analytical mathematicians. People readily accept the fact that doctors are human, they make mistakes and their medical decisions can be influenced by pharmaceutical marketing or by spurious squabbles with colleagues. One of my favorite TV shows was the American medical comedy Scrubs, which gave a surprisingly accurate portrayal of what it meant to work in a hospital. It was obviously fictional and contained many exaggerations to increase its comedic impact, but I could relate to many of the core themes presented in the show. The daily frustrations of being a physician-in-training or a senior attending physician, the fact that physicians make mistakes, the petty fights among physicians that can negatively impact their patients, the immense stress of having to deal with patients who cannot be helped, financial incentives for performing unnecessary medical procedures, physicians and nurses with substance abuse problems – these were all challenges that either I or my friends and colleagues had experienced.

One lone TV show such as Scrubs cannot be credited for taking down the “doctor mystique”, but it did provide a vehicle for us physicians to talk about the “dark side of medicine”. Speaking about flawed clinical decision-making and how personal emotions can affect our interactions with patients is not easy for physicians, because this form of introspection can lead to paralyzing guilt. All physicians know they make mistakes, and even though we ourselves do not buy into the “doctor mystique”, we may still feel the burden of having live up to it. I remember how I used to discuss some of the Scrubs episodes with other physicians and these light-hearted conversations about funny scenes in the TV show sometimes led to deeper discussions about our own personal experiences and the challenges we faced in our profession.

Being placed on a pedestal is a form of confinement. Dismantling mystiques not only liberates the individuals who are being mystified, but it can also benefit society as a whole. In the case of the doctor mystique, patients are now more likely to question the decisions of physicians, thus forcing doctors to explain why they are prescribing certain medications or expensive procedures. The internet enables patients to obtain information about their illnesses and treatment options. Instead of blindly following doctors’ orders, they want to engage their doctor in a discussion and become an integral part of the decision-making process.

The recognition that gifts, free dinners and honoraria paid by pharmaceutical companies strongly influence what medications doctors prescribe has led to the establishment of important new rules at universities and academic journals to curb this influence. Many medical schools now strongly restrict interactions between pharmaceutical company representatives and physicians-in-training. Academic journals and presentations at universities or medical conferences require a complete disclosure of all potential financial relationships that could impact the objectivity of the presented data. Some physicians may find these regulations cumbersome and long for the “mystique” days when their intentions were not under such scrutiny, but many of us think that these changes are making us better physicians and improving medical care.

As I watch many of these mystiques crumble, one mystique continues to persist: The Science Mystique. As with other mystiques, it consists of a collage of falsely idealized and idolized notions of what science constitutes. This mystique has many different manifestations, such as the firm belief that reported scientific findings are absolutely true beyond any doubt, scientific results obtained today are likely to remain true for all eternity and scientific research will be able to definitively solve all the major problems facing humankind. This science mystique is often paired with an over-simplified and reductionist view of science. Some popular science books, press releases or newspaper articles refer to scientists having discovered the gene or the molecule that is responsible for highly complex phenomena, such as cancer or philosophical constructs such as morality. When discussing a recent paper on wound healing, I came across an intriguing comment in a public comment thread: “When I read an article related to science it puts me in the mindset of perfection and credibility”. This is just one anecdotal comment, but I think that it captures the Science Mystique of people who place science on a pedestal of perfection.

As flattering as it may be, few scientists see science as encapsulating perfection. Even though I am a physician, most of my time is devoted to working as a cell biologist. My laboratory currently studies the biology of stem cells and the role of mitochondrial metabolism in stem cells. In the rather antiquated division of science into “hard” and “soft” sciences, where physics is considered a “hard” science and psychology or sociology are considered “soft” sciences, my field of work would be considered a middle-of-the-road, “firm” science. As cell biologists, we are able to conduct well-defined experiments, falsify hypotheses and directly test cause-effect relationships. Nevertheless, my experience with scientific results is that they are far from perfect and most good scientific work usually raises more questions than it provides answers. We scientists are motivated by our passion for exploration, and we know that even when we are able to successfully obtain definitive results, these findings usually point out even greater deficiencies and uncertainties in our knowledge. Stuart Firestein’s wonderful book “Ignorance: How It Drives Science” is a sincere and eloquent testimony to the key role of ignorance in scientific work. A thoughtful “I do not know the answer to this” uttered by a scientist is typically seen as a sign of scientific maturity, because it shows humility of the scientist and indicates a potential new direction for scientific research. On the other hand, when a scientist proudly proclaims to have found the most important gene or having defined the most important pathway for a certain biological process, it frequently indicates a lack of understanding of the complexity of the matter at hand.

One key problem of science is the issue of reproducibility. Psychology is currently undergoing a soul-searching process because many questions have been raised about why published scientific findings have such poor reproducibility when other psychologists perform the same experiments. One might attribute this to the “soft” nature of psychology, because it deals with variables such as emotions that are difficult to quantify and with heterogeneous humans as their test subjects. However, even pre-clinical cancer research on cancer cells and animal models of tumors is plagued by problems of reproducibility. In my work as a stem cell biologist, I have also encountered reproducibility issues when my laboratory has attempted to replicate published scientific findings. My experience in recent years has been that roughly only half of the published findings in stem cell biology can be reproduced when we attempt to conduct experiments according to the scientific methods and protocols of the published paper.

This anecdotal estimate of 50% reproducibility is not a comprehensive analysis. Researchers only attempt to replicate findings which are highly relevant to their work and which are published in a select group of scientific journals. If we tried to replicate every single paper in the field of stem cell biology, the success rate might be even lower. On the other hand, we devote a limited amount of time and resources to replicating results, because there is no funding available for replication experiments. It is possible that if we devoted enough time and resources to replicate a published study, tinkering with the different methods, trying out different batches of stem cells and reagents, we might have a higher likelihood of being able to replicate the results. Since negative studies are difficult to publish, these failed attempts at replication are buried and the published papers that cannot be replicated are rarely retracted. When scientists meet at conferences, they often informally share their respective experiences regarding their attempts to replicate research findings. These casual exchanges can be very helpful, because they help us ensure that we do not waste resources to build new scientific work on the shaky foundations of scientific papers that cannot be replicated.

In addition to knowing that a significant proportion of published scientific findings cannot be replicated, scientists are also aware of the fact that scientific knowledge is dynamic. Technologies used to acquire scientific data are continuously changing and the new scientific data amassed during any single year by far outpaces the capacity of scientists to fully understand and analyze it. Most scientists are currently struggling to keep up with the new scientific knowledge in their own field, let alone put it in context with the existing literature. As I have previously pointed out, more than 30-40 scientific papers are published on average on any given day in the field of stem cell biology. This overwhelming wealth of scientific information inevitably leads to a short half-life of scientific knowledge, as Samuel Arbesman has expressed in his book “The Half-Life of Facts”. What is considered a scientific fact today may be obsolete within five years. The books by Firestein and Arbesman are shining examples among the plethora of recent popular science books, because they explain why scientific knowledge is so ephemeral and yet so important. Hopefully, these books will help deconstruct the Science Mystique.

One aspect of science that receives comparatively little attention in popular science discussions is the human factor. Scientific experiments are conducted by scientists who have human failings, and thus scientific fallibility is entwined with human fallibility. Some degree of limited scientific replicability is intrinsic to the subject matter itself. Researchers use many different chemicals and biological reagents for their experiments, and even if they are obtained from the same manufacturer, there is no guarantee that their potency will be the same over time. At other times, researchers may make unintentional mistakes in interpreting their data or may unknowingly use contaminated samples. One can hardly blame scientists for heterogeneity of their tested samples or for making honest errors. However, there are far more egregious errors made by scientists that can have a major impact on how science is conducted. There are cases of outright fraud, where researchers just manufacture non-existent data, but these tend to be rare. When colleagues and scientific journals or organizations become aware of these cases of fraud, published papers are retracted and scientists face punitive measures. Such overt fraud tends to be unusual, and of the hundred or more scientific colleagues who I have personally worked with, I do not know of any one that has committed such fraud. However, what occurs far more frequently than overt fraud is the gentle fudging of scientific data, consciously or subconsciously, so that desired scientific results are obtained. Experimental outliers might be excluded using questionable justifications, especially if excluding them helps direct the data in the desired direction. Like most humans, scientists also have biases and would like to interpret their data in a manner that fits with their existing concepts and ideas.

Human fallibility not only affects how scientists interpret and present their data, but can also have a far-reaching impact on which scientific projects receive research funding or the publication of scientific results. When manuscripts are submitted to scientific journals or when grant proposal are submitted to funding agencies, they usually undergo a review by a panel of scientists who work in the same field and can ultimately decide whether or not a paper should be published or a grant funded. One would hope that these decisions are primarily based on the scientific merit of the manuscripts or the grant proposals, but anyone who has been involved in these forms of peer review knows that, unfortunately, personal connections or personal grudges can often be decisive factors.


Lack of scientific replicability, knowing about the uncertainties that come with new scientific knowledge, fraud and fudging, biases during peer review – these are all just some of the reasons why scientists rarely believe in the mystique of science. When I discuss this with acquaintances who are non-scientists, they sometimes ask me how I can love science if I have encountered these “ugly” aspects of science. My response is that I love science despite this “ugliness”, and perhaps even because of its “ugliness”. The fact that scientific knowledge is dynamic and ephemeral, the fact that we do not need to feel embarrassed about our ignorance and uncertainties, the fact that science is conducted by humans and is infused with human failings, these are all reasons to love science. When I think of science, I am reminded of the painting “Basket of Fruit” by Caravaggio, which is a still-life of a fruit bowl, but unlike older still-life paintings of fruit, it showed discolored and decaying leaves and fruit. The beauty and ingenuity of Caravaggio’s painting lies in its ability to show fruit how it really is, not the idealized fruit baskets that other painters would so often depict.

The challenge that we scientists face is to share our love for science despite its imperfections with those around us who do not actively work in the field of science. I remember speaking to a colleague of mine in the context of a wonderful spoof of a Lady Gaga song called “Bad Project”. We both agreed that the spoof was spot on, showing frustrations of a PhD student not being able to get experiments to work, having to base experiments on poorly documented lab note books and the tedious nature of scientific work. My colleague was concerned that if such spoofs ridiculing laboratory work became too common, it would embolden the American anti-science movement that is already very strong. Anyone who closely follows American science politics knows that creationists and global-warming deniers are constantly looking for opportunities to find flaws in scientific studies and that they use occasional errors as opportunities to suggest that well-established and replicated scientific results or theories should be discarded.

My response to these concerns is that it is our job as scientists to convince fellow citizens how important science is, despite its limitations and flaws. The uncertainties and limitations of scientific knowledge are not weaknesses, but strengths of the scientific approach, highlighting why it is so well-suited to help us understand our world. Enabling a false mystique of science being definitive and perfect is not going to benefit science or society in the long run. Instead, recognizing our failings and limitations in science and openly discussing them with our fellow citizens is going to help us improve how we conduct science. Anyone who carefully looks at Caravaggio’s “imperfect” painting can see its beauty and still fall in love with it. I hope that we scientists will be able to share the Caravaggio view of science with the general public.

Acknowledgement: An earlier version of this article was first published on 3quarksdaily.com.

Image Credits: Painting Basket of Fruit by Caravaggio via Wikimedia Commons

Mitochondrial Movements in Cancer

Research projects evolve in a fortuitous manner, often guided by a convergence of novel observations, intuition, helpful colleagues and unique personal circumstances. It is precisely this constellation that prompted two cardiologists to study the mitochondrial networks in lung cancer cells.

In 2008, my colleague and friend Stephen Archer, a Professor of Medicine at the University of Chicago, asked me whether I would be interested in studying the role of mitochondrial networks in lung cancer cells. My first response was the question “Do mitochondria really form networks?”, because at that time the expression “mitochondria” evoked images of scattered oval-like organelles, a textbook image of electron microscopy.

I was also intrigued by my colleague’s request, since we were both cardiologists and it therefore appeared to be somewhat unusual for us to study cancer cells. However, as is often the case in science research, personal motivations lay behind Stephen’s newfound research interest – Stephen’s cousin had recently died from lung cancer.

His cousin’s untimely death and Stephen’s frustration at the lack of therapeutic options for lung cancer victims had served as an incentive for him to expand his ongoing work on the role of mitochondria in cardiovascular cells to also include the investigation of mitochondria in cancer cells. Could we contribute to the identification of novel approaches to treat lung cancer?

During the preceding years, Stephen had focused on the role of glucose oxidation in cancer, in part inspired by the work of the German Nobel prize laureate Otto Heinrich Warburg (1883-1970). In the 1920s, Warburg hypothesized that cancer cells primarily rely on non-oxidative glycolysis instead of glucose oxidation to fuel their energy demands.This metabolic signature of cancer cells was critical for the development and growth of tumors.

As he examined the metabolism of malignant lung cancer cells and non-malignant healthy epithelial cells, Stephen had noticed an important difference in the physical appearance of the mitochondria. The mitochondria in the vast majority of cancer cells appeared to be small and fragmented, while healthy epithelial cells predominantly contained elongated, filamentous-like mitochondria that formed large intact networks. The cause and significance of this difference in the mitochondrial structure between lung cancer cells and healthy lung epithelial cells was unknown and thus a fertile ground for new discoveries.

Even though the planned collaborative project would primarily focus on the mitochondrial network structure and not the mitochondrial metabolism of cancer cells, I also decided to read some of the original Warburg papers in the original German language. German used to be a major language of scientific communication and publication in the 19th century as well as the first half of the 20th century. However, during the latter half of the 20th century and especially in the 21st century, English has become the predominant language of the scientific enterprise, even in Germany.

My nostalgic longing for reading scientific articles in German and my curiosity about how scientists wrote articles in the 1920s prompted me to download some of the Warburg papers. I have to admit that I was quite impressed by the comprehensive nature of the work described. The paper entitled “Über den Stoffwechsel der Carcinomzelle” (Biochemische Zeitschrift 152, 309-344 (1924)) by Warburg and his co-authors Karl Posener and Erwin Negelein contains a comprehensive evaluation of the respiration of tissues from multiple organs, such as the epithelium, connective tissue, brain tissue, retina and various benign and malignant tumors. This 36 page paper includes numerous hypotheses, observations and conclusions about the nature of tumor metabolism that would inspire subsequent generations of scientists.

One observation made by Warburg, for example, toward the end of the manuscript is that tumors with high levels of glycolysis are also associated with high levels of ammonia production and Warburg refers to this observation as an oddity that needs further research. It would take at least 80 years for researchers to understand some of the key underlying molecular mechanisms that explain this observation, when multiple research groups demonstrated that cancer cells use the amino acid glutamine as a major mitochondrial substrate and which upon degradation releases ammonia.

After reading the awe-inspiring Warburg papers, I felt even more enthusiastic about embarking on this new collaboration to study mitochondrial networks in cancer cells.

Peter Toth, a pharmacologist and neuroscientist who directed the confocal microscopy imaging core in Stephen’s group, used his extraordinary live-cell imaging expertise to visualize the mitochondrial networks of malignant and non-malignant lung cells over time. The microscopy data showed that the mitochondrial networks of cells were highly dynamic, continuously undergoing mitochondrial fission (fragmentation or division) and mitochondrial fusion (rejoining). However, at any given time, the majority of cancer cells had smaller, fragmented mitochondria when compared to healthy lung epithelial or vascular cells.

Working with a number of colleagues in our laboratories, we determined that lung cancer cells expressed higher levels of the mitochondrial fission protein Drp-1 when compared to multiple healthy cell types found in the lung. Inhibition of Drp-1 reversed the mitochondrial fragmentation and restored the degree of mitochondrial networking in malignant cancer cells to the levels we observed in healthy non-malignant cells. Similarly, over- expression of the mitochondrial fusion mediator Mitofusin-2 (Mfn-2) also increased mitochondrial networking. Importantly, inhibiting mitochondrial fission resulted in a cell cycle arrest of cancer cells and markedly reduced cancer cell proliferation. In vivo experiments using a tumor xenotransplant model showed a marked reduction in tumor progression when tumors were either treated with a pharmacological inhibitor of Drp-1 or when Mfn-2 was over-expressed.

Our findings are consistent with the observation that mitochondria undergo a cycle of fission and fusion which is coordinated with the cycle of cell division (mitosis). Our experiments suggest that targeting the mitotic fission of mitochondria may be a complementary approach to halt cancer cell proliferation. When we examined the tumor tissues of lung cancer patients, we found that tumor regions indeed expressed markedly higher levels of Drp-1 than healthy lung tissues. Whether Drp-1 levels are also higher in other forms of cancer and whether targeting mitochondrial fission in these other tumor tissues would be equally beneficial still needs to be examined in future studies.

Prior studies have detailed the role of Drp-1 in non-malignant cells where the protein appears to play a role in cell death. Drp-1 induced mitochondrial fission is a characteristic of mitochondrial apoptosis and short-term inhibition of Drp-1 can actually prevent cell death. However, other studies have also linked Drp-1 activation and mitochondrial fission to cell proliferation to mitochondrial fission because the cell cycle regulator Cdk1/Cyclin B regulates the activity of the mitochondrial fission mediator Drp-1. This suggests that mitochondrial fission induced by Drp-1 has two very distinct and nearly contradictory roles: cell death and cell growth.

In the highly proliferative cancer cells that we studied, Drp-1 appeared to be primarily acting as a mediator of mitotic fission, but it is quite possible that in other cell types or settings, Drp-1 may be more closely tied to regulation of apoptotic fission. The fact that the same protein regulates seemingly opposite processes of apoptotic fission during cell death and mitotic fission during cell proliferation may seem surprising. However, it is also reminiscent of the fact that mitochondria themselves can have apparently contradictory roles in cells, acting both as metabolic powerhouses as well as initiators of cell death.

From an evolutionary and teleological standpoint, a cell undergoing division (mitosis) would want to coordinate this process with the dividing and distributing of its mitochondrial organelles. Intact mitochondrial networks are probably difficult to distribute to daughter cells, whereas smaller, fragmented (“fissioned”) mitochondria can be easily distributed. Our study suggests that a reverse signal also exists, by which halting the mitochondrial fission seems to also halt the progression of the cell cycle.

As with any research, our study also points towards many unanswered questions, some of them highlighting the importance of how the nucleus communicates with other organelles: what are the specific mechanisms by which preventing mitotic mitochondrial fission signals back to the nucleus and halts the progression of the cell cycle? How does the cell coordinate the dynamics of other organelles during cell cycle? Could the dynamics of other organelles also be therapeutically targeted in cancer cells?

This work is only the beginning of a journey into the still mysterious realm of organelle movements in cancer cells. It may lead to new treatments for cancer, but such treatments would still require an extensive amount of additional work in pre-clinical studies before they could be tested in humans. The research may also provide fundamental insights of how a cell's nucleus, its "command center", interacts with the other organelles in the cell, some of which hold the keys to the survival and well-being of their "command center". The endosymbiont theory of cellular evolution states that organelles such as mitochondria are derived from lone bacteria (prokaryotes) which were engulfed by complex cells (eukaryotes). Too often, this relationship is portrayed in a one-sided manner: The endosymbiotic mitochondria are like slaves of the cell, continuously providing valuable metabolites for the growth of the cell.  However, it is also known that mitochondria can initiate cell death and that mitochondrial welfare is essential for the survival of the whole cell. The newly discovered role of mitochondrial dynamics in cancer cells, that merely preventing mitochondria from breaking up can bring the whole process of cell growth to a halt, underscores the importance of continuously re-evaluating the relationships and communication routes between the different organelles and the nucleus within a cell.

Notes: An earlier version of this article above was first published on the Scientific American blog. The scientific work described above was published in the FASEB Journal in an article entitled “Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer”. 

Jalees Rehman, Hannah J. Zhang, Peter T. Toth, Yanmin Zhang, Glenn Marsboom, Zhigang Hong, Ravi Salgia, Aliya N. Husain, Christian Wietholt, & Stephen L. Archer (2012). Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer FASEB Journal DOI: 10.1096/fj.11-196543

Professor Hands Out "Erase Undesirable Data Points" Coupons To PhD Students

TIJUANA- Obtaining a PhD in the life sciences now routinely takes six or seven years, whereas 30 or 40 years ago, students could graduate from a PhD program in just 3 or 4 years. The University of California, Tijuana (UCT) hired a consultancy firm to help them identify the reasons for the prolonged PhD duration. The consultants found the culprit: Data outliers.

Richard ("Dick") Tator is a Professor for Complementary and Alternative Science (CAS) at UCT and explains the findings.

“If a PhD student conducts an experiment with eight mice and five respond one way, but three mice the opposite way, most students then have to conduct additional experiments with many more mice to obtain a definitive, statistically significant result. This can prolong the duration of a PhD by months or even years.”

Professor Tator has now come up with a very innovative program to address this problem. He hands out “coupons” to his students which allow them to simply erase any data points which are interfering with the statistical significance of the results or which do not conform with the anticipated findings.

Lay Zee is a student in Professor Tator’s laboratory and is a big fan of the new system. “Dick is just a wonderful mentor. He basically allows every graduate student to earn up to three coupons a year, and each coupon is good for up to two years. So you do not have to use them all up at once and you can keep them in stock for a future data point that does not support your hypothesis.”

Lay says that Professor Tator gives out one “erase undesirable data coupon” for performing three chores, such as walking his dog, picking up Professor Tator’s laundry and baby-sitting his children. Lay feels that implementing “erase undesirable data coupons” is a win-win situation for everyone.

“I get to graduate sooner and we get to publish our results faster. Some of my friends in other programs are going to be stuck in their PhD program for another two or three years, performing mundane experiments, just to ensure that they will have statistically valid results, whereas I am already receiving job offers.”

Tator’s colleagues are also impressed with his innovative approach. Knott Eggsist is a professor of philosophy and UCT and admits that he is a bit envious.

“Professors in the humanities also have dogs that need to be walked and our students are also stuck in a PhD program for a very long time, sometimes as long as 8 or 9 years. We would love to have something similar to Dick’s coupons, but our problem is that we do not really have any actual data in the humanities.”

“How do you erase a data point that never even existed?”, Eggsist asks. After a brief pause, his eyes light up and he then nods vigorously, “Now that would be a great dissertation topic!”

Eggsist then talks about an equally innovative program that his department might implement.

“We are considering an entirely different approach in the philosophy department. We have determined that PhD in philosophy is prolonged unnecessarily because one has to deal with all the complex and long-winded thoughts of German philosophers. We will therefore start using an ‘Erase a German philosopher coupon’. With each coupon, our students will be able to write their dissertation and pretend that for example Hegel, Kant or Nietzsche or any other German philosopher of their choosing never existed and simply ignore all their writings.”

Open Science and Access to Medical Research

Juggling on the Berlin Wall
Wikimedia / Yann

It is rather odd how often I hear the expression paradigm shift during contemporary scientific presentations and seminars. The expression was popularized by Thomas Kuhn’s book "The Structure of Scientific Revolutions". In that book, Kuhn referred to ground-breaking and revolutionary changes in scientific thought as paradigm shifts, but the expression is so over-used today that even minor discoveries are sometimes marketed as paradigm shifts.

However, once in a while a true paradigm shift does come along and I believe we are currently witnessing such an emerging paradigm shift: open science. This concept entails that research results should be freely and openly accessible to the broad scientific colleagues as well as the public.

The idea of open science goes beyond merely providing public access to published scientific articles because it also includes offering access to the original research data. This would permit fellow researchers to help evaluate and analyze the results, so that the broader scientific community as well as the public can weigh in on the interpretation of the scientific findings. This aspect of open science likely does qualify for being a true paradigm shift, because it will require that we think of ourselves as part of research communities and usher in “networked discovery”, as has been described in a recent book by Michael Nielsen and discussed by Bora Zivkovic.

There are still many obstacles that need to be addressed before “open science” becomes generally accepted. Academic publishers currently reap significant profits from selling high-priced annual subscriptions to academic institutions, and they would lose this income if scientists started publishing their results in open-access journals that freely provide articles to readers without charging for subscriptions or per-article fees. Furthermore, academic institutions and individual scientists may be concerned about how they would apply for patents, if the discovery process is networked and involves score sof collaborating scientists.

Marc Kuchner recently wrote about how individual academic careers are currently built on marketing or branding oneself as a leader in defined research areas. If data and research methodologies are openly shared, it becomes much harder for individual investigators to take credit for discoveries and succeed in the competitive academic rat-race. Therefore, the current academic environment does not reward or provide incentives for openly sharing data or research methods.

Nevertheless, under pressure from the public and funding agencies that rightfully demand public access to the results of the funded research, it is likely that our current research culture will change. We will gradually tear down the walls that exist in our current scientific culture. It will not happen overnight, and we will have to develop new infrastructures to share scientific data, novel ways to assess academic success and reward contributions of individual scientists as well as establish high quality open access journals in a variety of scientific areas.

However, one has to keep in mind that certain areas of research are associated with unique challenges when it comes to the implementation of open science. The obstacles presented openly sharing original data and results in biomedical research may be very different from those in astrophysics.

Clinical research is often funded by the private industry and may thus evade mandates of public funding agencies or not-for-profit foundations to publish in open access journals and openly share results. But even publicly funded biomedical research is characterized by some unique challenges.

One such challenge is the importance of maintaining patient confidentiality when it comes to data sharing. Institutional Review Boards monitor the ethics of studies involving human subjects or patients at all academic institutions and one of their biggest concerns is how personal data of subjects or patients is handled. Usually, the data is de-identifed for the purpose of publication so that any kind of description of the disease state, symptoms, mutations or other findings cannot be linked to individuals.

Only a very small group of trained professionals have access to the names of the subjects or patients and usually only these review the medical charts or personal questionnaires of the participants. If the data-sets are made publicly available, it is imperative that appropriate safeguards are put in place to assure the participants that the data will only be shared in a de-identified format and that anybody seeing the data-set will not be able to link the diseases to the individual identity of the participants.

There is another critical obstacle that needs to be addressed when open science is implemented in medical research. The primary target audience for basic research that is not related to medicine or health consists of fellow scientists and science journalists.

I remember that I started my research career working as a chronobiologist on the circadian rhythms of the unicellular marine algae Gonyaulax polyedra. I doubt that anyone other than fellow scientists or science journalists would have been interested in accessing or interpreting our original data, even if all the data and results had been presented in an open access format.

On the other hand, my research in recent years has shifted to areas that have a more direct medical relevance, such as metabolism and stem cells in vascular disease, heart failure and cancer. My research approach is still focused on basic biological mechanisms, but due to the change in my research topics, I have encountered much broader interest from patients as well as healthcare providers.

Patients with severe chronic illnesses and their loved ones scour the internet for possible new therapies, even if these therapies have not been proven to work. The burden of disease makes them emotionally vulnerable so that they may selectively read and interpret the scientific literature in a manner that gives them false hopes.

For example, I remember talking to one of my heart failure patients who wanted to pay out of his own pocket for a trip to Thailand so that he could receive adult stem cell injections to improve his heart failure. He had found out about this experimental therapy through the internet. Since he did not qualify for any of the ongoing adult stem cell therapy trials in the US, he was extremely interested in trying out this therapy that was being offered overseas (for a substantial fee). He was not aware of the potential side effects of invasive stem cell injections or the importance of quality control and he assumed that it was proven that they work for heart failure. It was only after extensive counseling that he understood there was no clear evidence supporting the therapy and decided to avoid subjecting himself to the questionable therapy.

Many healthcare providers such as practicing physicians do not have a scientific background and are not necessarily trained to critically evaluate research data. They currently rely on review articles or meta-analyses published in respected journals, but they are also influenced by scientific data that are presented to them by representatives or consultants for the pharmaceutical industry.

At first glance, open access to original data sets should increase the transparency of research. However, if we remember the adage that “we only see what we want to see”, we have to realize that open access to research data will also create an opportunity for pharmaceutical companies or for-profit hospitals to promote medical therapies on the basis of limited scientific data.

Selective reporting of the publicly available data by special interest groups could find an excellent breeding ground among emotionally vulnerable patients or healthcare providers who may be easily swayed by the plight and hopes of their patients. One example of selective reporting or selective analysis would be when negative clinical trials are re-analyzed to identify some subgroups of patients that showed a statistically significant improvement with the experimental therapy.

Another example could be that the clinical significance of in vitro cell signaling studies or animal studies could be over-stated. In a traditional academic paper, most of our scientific colleagues (voluntarily or after peer-review) highlight the limitations of their studies. If the data is publicly available, the data would be open to variant interpretations, even by members of the community who are not trained to appropriately interpret the data.

The solution to these potential issues that may arise when we transition to an open science format is not to limit the access of the data. Instead, it is imperative that concomitant with the creation of an open science environment we also build independent institutions or organizations that help interpret the available the data in a manner that non-scientists are able to receive accurate and solid information about the nature and significance of the results.

“Consumer Reports” in the US or “Stiftung Warentest” in Germany routinely test consumer products for their quality and safety, and report them in a manner that members of public can understand the results. Consumers buy subscriptions to their websites or magazines and they enjoy respect among consumers, who have confidence in their unbiased evaluations of products.

One could envision similar institutions that evaluate the biomedical research data and can give solid advice to non-specialists. Ideally, such institutions would need to include independent expert scientists as well as independent experts at communicating science to the broader public. The reason for including expertise in science reporting and science communication is simply due to the fact that many scientists are “communicatively challenged”. It does not help the broader public if a group of scientists charged with providing independent evaluation of publicly available datasets produces reports that are full of technical jargon. As funding agencies and the public push for open access to scientific research data, they also need to push for developing and funding infrastructures that can help the public interpret the openly accessible data.

In summary, I believe that the time for open science and networked discovery has arrived and that it will definitely enhance the progress of scientific research, as long as we build institutions that help us process and understand the flood of scientific data that will be released in the new open science world.

This article was originally published on the Scientific American Guest Blog