Less than one fifth of PhD students in the United States will be able to pursue tenure track academic faculty careers once they graduate from their program. Reduced federal funding for research and dwindling support from the institutions for their tenure-track faculty are some of the major reasons for why there is such an imbalance between the large numbers of PhD graduates and the limited availability of academic positions. Upon completing the program, PhD graduates have to consider non-academic job opportunities such as in the industry, government agencies and non-profit foundations but not every doctoral program is equally well-suited to prepare their graduates for such alternate careers. It is therefore essential for prospective students to carefully assess the doctoral program they want to enroll in and the primary mentor they would work with. The best approach is to proactively contact prospective mentors, meet with them and learn about the research opportunities in their group but also discuss how completing the doctoral program would prepare them for their future careers.
The vast majority of professors will gladly meet a prospective graduate student and discuss research opportunities as well as long-term career options, especially if the student requesting the meeting clarifies the goal of the meeting. However, there are cases when students wait in vain for a response. Is it because their email never reached the professor because it got lost in the internet ether or a spam folder? Was the professor simply too busy to respond? A research study headed by Katherine Milkman from the University of Pennsylvania suggests that the lack of response from the professor may in part be influenced by the perceived race or gender of the student.
Milkman and her colleagues conducted a field experiment in which 6,548 professors at the leading US academic institutions (covering 89 disciplines) were contacted via email to meet with a prospective graduate student. Here is the text of the email that was sent to each professor.
Subject Line: Prospective Doctoral Student (On Campus Next
Dear Professor [surname of professor inserted here],
I am writing you because I am a prospective doctoral student with considerable interest in your research. My plan is to apply to doctoral programs this coming Fall, and I am eager to learn as much as I can about research opportunities in the meantime.
I will be on campus next Monday, and although I know it is short notice, I was wondering if you might have 10 minutes when you would be willing to meet with me to briefly talk about your work and any possible opportunities for me to get involved in your research. Any time that would be convenient for you would be fine with me, as meeting with you is my first priority during this campus visit.
Thank you in advance for your consideration.
[Student’s full name inserted here]
As a professor who frequently receives emails from people who want to work in my laboratory, I feel that the email used in the research study was extremely well-crafted. The student only wants a brief meeting to explore potential opportunities without trying to extract any specific commitment from the professor. The email clearly states the long-term goal – applying to doctoral programs. The tone is also very polite and the student expresses willingness of the prospective student to a to the professor’s schedule. Each email was also personally addressed with the name of the contacted faculty member.
Milkman’s research team then assessed whether the willingness of the professors to respond depended on the gender or ethnicity of the prospective student. Since this was an experiment, the emails and student names were all fictional but the researchers generated names which most readers would clearly associate with a specific gender and ethnicity.
Here is a list of the names they used:
White male names: Brad Anderson, Steven Smith
White female names: Meredith Roberts, Claire Smith
The researchers assessed whether the professors responded (either by agreeing to meet or providing a reason for why they could not meet) at all or whether they simply ignored the email and whether the rate of response depended on the ethnicity/gender of the student.
The overall response rate of the professors ranged from about 60% to 80%, depending on the research discipline as well as the perceived ethnicity and gender of the prospective student. When the emails were signed with names suggesting a white male background of the student, professors were far less likely to ignore the email when compared to those signed with female names or names indicating an ethnic minority background. Professors in the business sciences showed the strongest discrimination in their response rates. They ignored only 18% of emails when it appeared that they had been written by a white male and ignored 38% of the emails if they were signed with names indicating a female gender or ethnic minority background. Professors in the education disciplines ignored 21% of emails with white male names versus 35% with female or minority names. The discrimination gaps in the health sciences (33% vs 43%) and life sciences (32% vs 39%) were smaller but still significant, whereas there was no statistical difference in the humanities professor response rates. Doctoral programs in the fine arts were an interesting exception where emails from apparent white male students were more likely to be ignored (26%) than those of female or minority candidates (only 10%).
The discrimination primarily occurred at the initial response stage. When professors did respond, there was no difference in terms of whether they were able to make time for the student. The researchers also noted that responsiveness discrimination in any discipline was not restricted to one gender or ethnicity. In business doctoral programs, for example, professors were most likely to ignore emails with black female names and Indian male names. Significant discrimination against white female names (when compared to white males names) predicted an increase in discrimination against other ethnic minorities. Surprisingly, the researchers found that having higher representation of female and minority faculty at an institution did not necessarily improve the responsiveness towards requests from potential female or minority students.
This carefully designed study with a large sample size of over 6,500 professors reveals the prevalence of bias against women and ethnic minorities at the top US institutions. This bias may be so entrenched and subconscious that it cannot be remedied by simply increasing the percentage of female or ethnic minority professors in academia. Instead, it is important that professors understand that they may be victims of these biases even if they do not know it. Something as simple as deleting an email from a prospective student because we think that we are too busy to respond may be indicative of an insidious gender or racial bias that we need to understand and confront. Increased awareness and introspection as well targeted measures by institutions are the important first steps to ensure that students receive the guidance and mentorship they need, independent of their gender or ethnic background.
Milkman KL, Akinola M, & Chugh D (2015). What happens before? A field experiment exploring how pay and representation differentially shape bias on the pathway into organizations. The Journal of applied psychology, 100 (6), 1678-712 PMID: 25867167
Hearing about the HannoverGEN project made me feel envious and excited. Envious, because I wish my high school had offered the kind of hands-on molecular biology training provided to high school students in Hannover, the capital of the German state of Niedersachsen. Excited, because it reminded me of the joy I felt when I first isolated DNA and ran gels after restriction enzyme digests during my first year of university in Munich. I knew that many of the students at the HannoverGEN high schools would be similarly thrilled by their laboratory experience and perhaps even pursue careers as biologists or biochemists.
What did HannoverGEN entail? It was an optional pilot program initiated and funded by the state government of Niedersachsen at four high schools in the Hannover area. Students enrolled in the HannoverGEN classes would learn to use molecular biology tools typically reserved for college-level or graduate school courses in order to study plant genetics. Some of the basic experiments involved isolating DNA from cabbage or how learning how bacteria transfer genes to plants, more advanced experiments enabled the students to analyze whether or not the genome of a provided maize sample had been genetically modified. Each experimental unit was accompanied by relevant theoretical instruction on the molecular mechanisms of gene expression and biotechnology as well as ethical discussions regarding the benefits and risks of generating genetically modified organisms (“GMOs”). The details of the HannoverGEN program are only accessible through the the Wayback Machine Internet archive because the award-winning educational program and the associated website were shut down in 2013 at the behest of German anti-GMO activist groups, environmental activists, Greenpeace, the Niedersachsen Green Party and the German organic food industry.
Why did these activists and organic food industry lobbyists oppose a government-funded educational program which improved the molecular biology knowledge and expertise of high school students? A press release entitled “Keine Akzeptanzbeschaffung für Agro-Gentechnik an Schulen!” (“No Acceptance for Agricultural Gene Technology at Schools“) in 2012 by an alliance representing “organic” or “natural food” farmers accompanied by the publication of a critical “study” with the same title (PDF), which was funded by this alliance as well as its anti-GMO partners, gives us some clues. They feared that the high school students might become too accepting of biotechnology in agriculture and that the curriculum did not sufficiently highlight all the potential dangers of GMOs. By allowing the ethical discussions to not only discuss the risks but also mention the benefits of genetically modifying crops, students might walk away with the idea that GMOs could be beneficial for humankind. The group believed that taxpayer money should not be used to foster special interests such as those of the agricultural industry which may want to use GMOs.
A response by the University of Hannover (PDF), which had helped develop the curriculum and coordinated the classes for the high school students, carefully analyzed the complaints of the anti-GMO activists. The author of the anti-HannoverGEN “study” had not visited the HannoverGEN laboratories, nor had he had interviewed the biology teachers or students enrolled in the classes. In fact, his critique was based on weblinks that were not even used in the curriculum by the HannoverGEN teachers or students. His analysis ignored the balanced presentation of biotechnology that formed the basis of the HannoverGEN curriculum and that discussing potential risks of genetic modification was a core topic in all the classes.
Unfortunately, this shoddily prepared “study” had a significant impact, in part because it was widely promoted by partner organizations. Its release in the autumn of 2012 came at an opportune time for political activists because Niedersachsen was about to have an election. Campaigning against GMOs seemed like a perfect cause for the Green Party and a high school program which taught the use of biotechnology to high school students became a convenient lightning rod. When the Social Democrats and the Green Party formed a coalition after winning the election in early 2013, nixing the HannoverGEN high school program was formally included in the so-called coalition contract. This is a document in which coalition partners outline the key goals for the upcoming four year period. When one considers how many major issues and problems the government of a large German state has to face, such as healthcare, education, unemployment or immigration, it is mind-boggling that de-funding a program involving only four high schools received so much attention that it needed to be anchored in the coalition contract. In fact, it is a testimony to the influence and zeal of the anti-GMO lobby.
Once the cancellation of HannoverGEN was announced, the Hannover branch of Greenpeace also took credit for campaigning against this high school program and celebrated its victory. The Greenpeace anti-GMO activist David Petersen said that the program was too cost intensive because equipping high school laboratories with state-of-the-art molecular biology equipment had already cost more than 1 million Euros. The previous center-right government which had initiated the HannoverGEN project was planning on expanding the program to even more high schools because of the program’s success and national recognition for innovative teaching. According to Petersen, this would have wasted even more taxpayer money without adequately conveying the dangers of using GMOs in agriculture.
The scientific community was shaken up by the decision of the new Social Democrat-Green Party coalition government in Niedersachsen. This was an attack on the academic freedom of schools under the guise of accusing them of promoting special interests while ignoring that the anti-GMO activists were representing their own special interests. The “study” attacking HannoverGEN was funded by the lucrative “organic” or “natural food” food industry! Scientists and science writers such as Martin Ballaschk or Lars Fischer wrote excellent critical articles stating that squashing high-quality, hand-on science programs could not lead to better decision-making. How could ignorant students have a better grasp of GMO risks and benefits than those who receive relevant formal science education and thus make truly informed decisions? Sadly, this outcry by scientists and science writers did not make much of a difference. It did not seem that the media felt this was much of a cause to fight for. I wonder if the media response would have been just as lackluster if the government had de-funded a hands-on science lab to study the effects of climate change.
In 2014, the government of Niedersachsen then announced that they would resurrect an advanced biology laboratory program for high schools with the generic and vague title “Life Science Lab”. By removing the word “Gen” from its title which seems to trigger visceral antipathy among anti-GMO activists, de-emphasizing genome science and by also removing any discussion of GMOs from the curriculum, this new program would leave students in the dark about GMOs. Ignorance is bliss from an anti-GMO activist perspective because the void of scientific ignorance can be filled with fear.
From the very first day that I could vote in Germany during the federal election of 1990, I always viewed the Green Party as a party that represented my generation. A party of progressive ideas, concerned about our environment and social causes. However, the HannoverGEN incident is just one example of how the Green Party is caving in to ideologies, thus losing its open-mindedness and progressive nature. In the United States, the anti-science movement, which attacks teaching climate change science or evolutionary biology at schools, tends to be rooted in the right wing political spectrum. Right wingers or libertarians are the ones who always complain about taxpayer dollars being wasted and used to promote agendas in schools and universities. But we should not forget that there is also a different anti-science movement rooted in the leftist and pro-environmental political spectrum – not just in Germany. As a scientist, I feel that it is becoming increasingly difficult to support the Green Party because of its anti-science stance.
I worry about all anti-science movements, especially those which attack science education. There is nothing wrong with questioning special interests and ensuring that school and university science curricula are truly balanced. But the balance needs to be rooted in scientific principles, not political ideologies. Science education has a natural bias – it is biased towards knowledge that is backed up by scientific evidence. We can hypothetically discuss dangers of GMOs but the science behind the dangers of GMO crops is very questionable. Just like environmental activists and leftists agree with us scientists that we do not need to give climate change deniers and creationists “balanced” treatment in our science curricula, they should also accept that much of the “anti-GMO science” is currently more based on ideology than on actual scientific data. Our job is to provide excellent science education so that our students can critically analyze and understand scientific research, independent of whether or not it supports our personal ideologies.
Anti-Semitism and the holocaust are among the central themes in the modern German secondary school curriculum. During history lessons in middle school, we learned about anti-Semitism and the persecution of Jews in Europe during the middle ages and early modernity. Our history curriculum in the ninth and tenth grades focused on the virulent growth of anti-Semitism in 20th century Europe, how Hitler and the Nazi party used anti-Semitism as a means to rally support and gain power, and how the Nazi apparatus implemented the systematic genocide of millions of Jews.
In grades 11 to 13, the educational focus shifts to a discussion of the broader moral and political context of anti-Semitism and Nazism. How could the Nazis enlist the active and passive help of millions of “upstanding” citizens to participate in this devastating genocide? Were all Germans who did not actively resist the Nazis morally culpable or at least morally responsible for the Nazi horrors? Did Germans born after the Second World War inherit some degree of moral responsibility for the crimes committed by the Nazis? How can German society ever redeem itself after being party to the atrocities of the Nazis? Anti-Semitism and Nazism were also important topics in our German literature and art classes because the Nazis persecuted and murdered German Jewish intellectuals and artists, and because the shame and guilt experienced by Germans after 1945 featured so prominently in German art and literature.
One purpose of extensively educating Germany school-children about this dark and shameful period of German history is the hope that if they are ever faced with the reemergence of prejudice directed against Jews or any other ethnic or religious group, they will have the courage to stand up for those who are being persecuted and make the right moral choices. As such, it is part of the broader Vergangenheitsbewältigung (wrestling with one’s past) in post-war German society which takes place not only in schools but in various public venues. The good news, according to recent research published in the Proceedings of the National Academy of Sciences by Nico Voigtländer and Hans-Joachim Voth, is that Germans who attended school after the Second World War have shown a steady decline in anti-Semitism. The bad news: Vergangenheitsbewältigung is a bigger challenge for Germans who attended school under the Nazis because a significant proportion of them continue to exhibit high levels of anti-Semitic attitudes more than half a century after the defeat of Nazi Germany.
Voigtländer and Voth examined the results of the large General Social Survey for Germany (ALLBUS) in which several thousand Germans were asked about their values and beliefs. The survey took place in 1996 and 2006, and the researchers combined the results of both surveys with a total of 5,300 participants from 264 German towns and cities. The researchers were specifically interested in anti-Semitic attitudes and focused on three survey questions specifically related to anti-Semitism. Survey participants were asked to respond on a scale of 1 to 7 and indicate whether they thought Jews had too much influence in the world, whether Jews were responsible for their own persecution and whether Jews should have equal rights. The researchers categorized participants as “committed anti-Semites” if they revealed anti-Semitic attitudes to all three questions. The overall rate of committed anti-Semites was 4% in Germany but there was significant variation depending on the geographical region and the age of the participants.
Germans born in the 1970s and 1980s had only 2%-3% committed anti-Semites whereas the rate was nearly double for Germans born in the 1920s (6%). However, the researchers noted one exception: Germans born in the 1930s. Those citizens had the highest fraction of anti-Semites: 10%. The surveys were conducted in 1996 and 2006 when the participants born in in the 1930s were 60-75 years old. In other words, one out of ten Germans of that generation did not think that Jews deserved equal rights!
The researchers attributed this to the fact that people born in the 1930s were exposed to the full force of systematic Nazi indoctrination with anti-Semitic views which started as early as in elementary school and also took place during extracurricular activities such as the Hitler Youth programs. The Nazis came to power in 1933 and immediately began implementing a whole-scale propaganda program in all schools. A child born in 1932, for example, would have attended elementary school and middle school as well as Hitler Youth programs from age six onwards till the end of the war in 1945 and become inculcated with anti-Semitic propaganda.
The researchers also found that the large geographic variation in anti-Semitic prejudices today was in part due to the pre-Nazi history of anti-Semitism in any given town. The Nazis were not the only and not the first openly anti-Semitic political movement in Germany. There were German political parties with primarily anti-Jewish agendas which ran for election in the late 19th century and early 20th century. Voigtländer and Voth analyzed the votes that these anti-Semitic parties received more than a century ago, from 1890 to 1912. Towns and cities with the highest support for anti-Semitic parties in this pre-Nazi era are also the ones with the highest levels of anti-Semitic prejudice today. When children were exposed to anti-Semitic indoctrination in schools under the Nazis, the success of these hateful messages depended on how “fertile” the ground was. If the children were growing up in towns and cities where family members or public figures had supported anti-Jewish agenda during prior decades then there was a much greater likelihood that the children would internalize the Nazi propaganda. The researchers cite the memoir of the former Hitler Youth member Alfons Heck:
“We who were born into Nazism never had a chance unless our parents were brave enough to resist the tide and transmit their opposition to their children. There were few of those.”
The researchers then address the puzzling low levels of anti-Semitic prejudices among Germans born in the 1920s. If the theory of the researcher were correct that anti-Semitic prejudices persist today because Nazi school indoctrination then why aren’t Germans born in the 1920s more anti-Semitic? A child born in 1925 would have been exposed to Nazi propaganda throughout secondary school. Oddly enough, women born in the 1920s did show high levels of anti-Semitism when surveyed in 1996 and 2006 but men did not. Voigtländer and Voth solve this mystery by reviewing wartime fatality rates. The most zealous male Nazi supporters with strong anti-Semitic prejudices were more likely to volunteer for the Waffen-SS, the military wing of the Nazi party. Some SS divisions had an average age of 18 and these SS-divisions had some of the highest fatality rates. This means that German men born in the 1920s weren’t somehow immune to Nazi propaganda. Instead, most of them perished because they bought into it and this is why we now see lower levels of anti-Semitism than expected in Germans born during that decade.
A major limitation of this study is its correlational nature and the lack of data on individual exposure to Nazism. The researchers base their conclusions on birth years and historical votes for anti-Semitic parties of towns but did not track how much individuals were exposed to anti-Semitic propaganda in their schools or their families. Such a correlational study cannot establish a cause-effect relationship between propaganda and the persistence of prejudice today. One factor not considered by the researchers, for example, is that Germans born in the 1930s are also among those who grew up as children in post-war Germany, often under conditions of extreme poverty and even starvation.
Even without being able to establish a clear cause-effect relationship, the findings of the study raise important questions about the long-term effects of racial propaganda. It appears that a decade of indoctrination may give rise to a lifetime of hatred. Our world continues to be plagued by prejudice against fellow humans based on their race or ethnicity, religion, political views, gender or sexual orientation. Children today are not subject to the systematic indoctrination implemented by the Nazis but they are probably still exposed to more subtle forms of prejudice and we do not know much about its long-term effects. We need to recognize the important role of public education in shaping the moral character of individuals and ensure that our schools help our children become critical thinkers with intact moral reasoning, citizens who can resist indoctrination and prejudice.
Fareed Zakaria recently wrote an article in the Washington Post lamenting the loss of liberal arts education in the United States. However, instead of making a case for balanced education, which integrates various forms of creativity and critical thinking promoted by STEM (science, technology, engineering and mathematics) and by a liberal arts education, Zakaria misrepresents STEM education as primarily teaching technical skills and also throws in a few cliches about Asians. You can read my response to his article at 3Quarksdaily.
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.
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.
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.
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.
“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.
The professional animator and molecular biologist Janet Iwasa at Harvard Medical School is generating beautiful animations of cellular processes such as proteasome structure and function or endocytosis. Importantly, she has published these on her website with a Creative Commons license so that everyone has access to them. She has been interviewed by EarthSky, where she explains why she became a molecular animator.
When I remember the 80s, I think of Nena’s 99 Luftballons, Duran Duran’s Wild Boys and ….snake venom. Back in those days, I used to be a typical high school science nerd. My science nerdiness interfered with my ability to socialize with non-nerds and it was characterized by an unnecessary desire to read science books and articles that I did not really understand, just so that I could show off with some fancy science terminology. I did not have much of an audience to impress, because my class-mates usually ignored me. My high school biology teacher, Herr Sperr, was the only one who had the patience to listen to me. One of the science books that I purchased was called “Gehirn und Nervensystem” (i.e. “Brain and Nervous System”), published by Spektrum der Wissenschaft, the German publisher of Scientific American. It was a collection of Scientific American articles in the field of neuroscience that had been translated into German. I was thumbing through it, looking for some new neurobiology idea or expression that I could use to impress Herr Sperr. While browsing the book, I came across the article “Der Nervenwachstumsfaktor” (originally published in Scientific American as “The Nerve-Growth Factor” in 1979) by Rita Levi-Montalcini and Pietro Calissano.
My curiosity was piqued by this article, because I did not realize that nerves had “growth factors” and because one of the authors, Rita Levi-Montalcini, had just won the Nobel Prize in the preceding year. I started reading the article and loved it, reading it over and over again. I liked the article so much, that I did not even try to show off about it and kept the newly discovered inspiration to myself. There are many reasons why I loved the article and I will just mention two of them:
1. Scientific discovery is an exciting journey, starting and ending with unanswered questions
Levi-Montalcini and Calissano started off by describing the state of knowledge and the unanswered questions in the field of developmental neurobiology and neuronal differentiation in the 1940s, when Levi-Montalcini was about to launch her career as a scientist. They commented on how the simple yet brilliant idea to test whether tumors could influence the growth of nerves sparked a whole new field of investigation. They narrated a beautiful story of scientific discovery, from postulating a “nerve growth factor” to actually isolating and sequencing it. Despite all the advances that Levi-Montalcini and her colleagues had made, the article ended with a new mystery, that the role of the nerve growth factor may be much bigger than all the researchers suspected. The nerve growth factor was able to act on cells that were not neurons and it was unclear why this was the case. By hinting at these yet to be defined roles, the article made it clear that so much more work was necessary and I felt that an invitation was being extended to the readers to participate in the future discovery.
2. Scientific tools can harbor surprises and important clues
The article mentioned one important coincidence that helped shape the progress of discovering the sequence of the nerve growth factor. To assess whether the putative nerve growth factor contained nucleic acids, Levi-Montalcini and her colleagues exposed the “soup” that was inducing the growth of nerves to snake venom. The rationale was that snake venom (by the way, the German expression “Schlangengift” sounds even more impressive than the English “snake venom”) would degrade nucleic acids and if the growth enhancing properties disappeared, it would mean that the nerve growth inducing factor contained nucleic acids. It turned out that the snake venom unexpectedly magnified the nerve growth enhancing effects, because the venom contained large quantities of the nerve growth factor itself. This unexpected finding made it much easier for the researchers to sequence the nerve growth factor, because the snake venom now provided access to a large source of the nerve growth factor and it resulted in a new mystery: Why would snake venom contain a nerve growth factor?
In the subsequent decades, as I embarked on my own career as a scientist, I often thought about this article that I read back in high school. It inspired me to become a cell biologist and many of the projects in my laboratory today focus on the effects of growth factors on blood vessels and stem cells. The article also made me think about the importance of continuously re-evaluating the tools that we use. Sometimes our tools are not as neutral or straight-forward as we think, and this lesson is just as valid today as it was half a century ago. For example, a recent paper in Cell found that the virus used for reprogramming adult cells into stem cells is not merely a tool that allows entry of the reprogramming factors, as was previously thought. The virus tool can actually activate the stem cell reprogramming itself, reminiscent of how the “snake venom” tool was able to induce nerve growth.