Synthetic Biology: Engineering Life To Examine It

Two scientific papers that were published in the journal Nature in the year 2000 marked the beginning of engineering biological circuits in cells. The paper "Construction of a genetic toggle switch in Escherichia coli" by Timothy Gardner, Charles Cantor and James Collins created a genetic toggle switch by simultaneously introducing an artificial DNA plasmid into a bacterial cell. This DNA plasmid contained two promoters (DNA sequences which regulate the expression of genes) and two repressors (genes that encode for proteins which suppress the expression of genes) as well as a gene encoding for green fluorescent protein that served as a read-out for the system. The repressors used were sensitive to either selected chemicals or temperature. In one of the experiments, the system was turned ON by adding the chemical IPTG (a modified sugar) and nearly all the cells became green fluorescent within five to six hours. Upon raising the temperature to activate the temperature-sensitive repressor, the cells began losing their green fluorescence within an hour and returned to the OFF state. Many labs had used chemical or temperature switches to turn gene expression on in the past, but this paper was the first to assemble multiple genes together and construct a switch which allowed switching cells back and forth between stable ON and OFF states.

The same issue of Nature contained a second land-mark paper which also described the engineering of gene circuits. The researchers Michael Elowitz and Stanislas Leibler describe the generation of an engineered gene oscillator in their article "A synthetic oscillatory network of transcriptional regulators". By introducing three repressor genes which constituted a negative feedback loop and a green fluorescent protein as a marker of the oscillation, the researchers created a molecular clock in bacteria with an oscillation period of roughly 150 minutes. The genes and proteins encoded by the genes were not part of any natural biological clock and none of them would have oscillated if they had been introduced into the bacteria on their own. The beauty of the design lay in the combination of three serially repressing genes and the periodicity of this engineered clock reflected the half-life of the protein encoded by each gene as well as the time it took for the protein to act on the subsequent member of the gene loop.


Both papers described the introduction of plasmids encoding for multiple genes into bacteria but this itself was not novel. In fact, this has been a routine practice since the 1970s for many molecular biology laboratories. The panache of the work lay in the construction of functional biological modules consisting of multiple genes which interacted with each other in a controlled and predictable manner. Since the publication of these two articles, hundreds of scientific papers have been published which describe even more intricate engineered gene circuits. These newer studies take advantage of the large number of molecular tools that have become available to query the genome as well as newer DNA plasmids which encode for novel biosensors and regulators.

Synthetic biology is an area of science devoted to engineering novel biological circuits, devices, systems, genomes or even whole organisms. This rather broad description of what "synthetic biology" encompasses reflects the multidisciplinary nature of this field which integrates ideas derived from biology, engineering, chemistry and mathematical modeling as well as a vast arsenal of experimental tools developed in each of these disciplines. Specific examples of "synthetic biology" include the engineering of microbial organisms that are able to mass produce fuels or other valuable raw materials, synthesizing large chunks of DNA to replace whole chromosomes or even the complete genome in certain cells, assembling synthetic cells or introducing groups of genes into cells so that these genes can form functional circuits by interacting with each other. Synthesis in the context of synthetic biology can signify the engineering of artificial genes or biological systems that do not exist in nature (i.e. synthetic = artificial or unnatural), but synthesis can also stand for integration and composition, a meaning which is closer to the Greek origin of the word.  It is this latter aspect of synthetic biology which makes it an attractive area for basic scientists who are trying to understand the complexity of biological organisms. Instead of the traditional molecular biology focus on studying just one single gene and its function, synthetic biology is engineering biological composites that consist of multiple genes and regulatory elements of each gene. This enables scientists to interrogate the interactions of these genes, their regulatory elements and the proteins encoded by the genes with each other. Synthesis serves as a path to analysis.

One goal of synthetic biologists is to create complex circuits in cells to facilitate biocomputing, building biological computers that are as powerful or even more powerful that traditional computers. While such gene circuits and cells that have been engineered have some degree of memory and computing power, they are no match for the comparatively gigantic computing power of even small digital computers. Nevertheless, we have to keep in mind that the field is very young and advances are progressing at a rapid pace.
One of the major recent advances in synthetic biology occurred in 2013 when an MIT research team led by Rahul Sarpeshkar and Timothy Lu at MIT created analog computing circuits in cells.

Most synthetic biology groups that engineer gene circuits in cells to create biological computers have taken their cues from contemporary computer technology. Nearly all of the computers we use are digital computers, which process data using discrete values such as 0's and 1's. Analog data processing on the other hand uses a continuous range of values instead of 0's and 1's. Digital computers have supplanted analog computing in nearly all areas of life because they are easy to program, highly efficient and process analog signals by converting them into digital data. Nature, on the other hand, processes data and information using both analog and digital approaches. Some biological states are indeed discrete, such as heart cells which are electrically depolarized and then repolarized in periodical intervals in order to keep the heart beating. Such discrete states of cells (polarized / depolarized) can be modeled using the ON and OFF states in the biological circuit described earlier. However, many biological processes, such as inflammation, occur on a continuous scale. Cells do not just exist in uninflamed and inflamed states; instead there is a continuum of inflammation from minimal inflammatory activation of cells to massive inflammation. Environmental signals that are critical for cell behavior such as temperature, tension or shear stress occur on a continuous scale and there is little evidence to indicate that cells convert these analog signals into digital data.

Most of the attempts to create synthetic gene circuits and study information processing in cells have been based on a digital computing paradigm. Sarpeshkar and Lu instead wondered whether one could construct analog computation circuits and take advantage of the analog information processing systems that may be intrinsic to cells. The researchers created an analog synthetic gene circuit using only three proteins that regulate gene expression and the fluorescent protein mCherry as a read-out. This synthetic circuit was able to perform additions or ratiometric calculations in which the cumulative fluorescence of the mCherry was either the sum or the ratio of selected chemical input concentrations. Constructing a digital circuit with similar computational power would have required a much larger number of components.

The design of analog gene circuits represents a major turning point in synthetic biology and will likely spark a wave of new research which combines analog and digital computing when trying to engineer biological computers. In our day-to-day lives, analog computers have become more-or-less obsolete. However, the recent call for unconventional computing research by the US Defense Advanced Research Projects Agency (DARPA) is seen by some as one indicator of a possible paradigm shift towards re-examining the value of analog computing. If other synthetic biology groups can replicate the work of Sarpeshkar and Lu and construct even more powerful analog or analog-digital hybrid circuits, then the renaissance of analog computing could be driven by biology.  It is difficult to make any predictions regarding the construction of biological computing machines which rival or surpass the computing power of contemporary digital computers. What we can say is that synthetic biology is becoming one of the most exciting areas of research that will provide amazing insights into the complexity of biological systems and may provide a path to revolutionize biotechnology.

An earlier version of this article was first published at 3Quarksdaily.


Daniel R, Rubens JR, Sarpeshkar R, & Lu TK (2013). Synthetic analog computation in living cells. Nature, 497 (7451), 619-23 PMID: 23676681

Sharing Our Sorrow Via Facebook

Geteiltes Leid ist halbes Leid ("Shared sorrow is half the sorrow") is a popular German proverb which refers to the importance of sharing bad news and troubling experiences with others. The therapeutic process of sharing takes on many different forms: we may take comfort in the fact that others have experienced similar forms of sorrow, we are often reassured by the empathy and encouragement we receive from friends, and even the mere process of narrating the details of what is troubling us can be beneficial. Finding an attentive audience that is willing to listen to our troubles is not always easy. In a highly mobile, globalized world, some of our best friends may be located thousands of kilometers away, unable to meet face-to-face. The omnipresence of social media networks may provide a solution. We are now able to stay in touch with hundreds of friends and family members, and commiserate with them. But are people as receptive to sorrow shared via Facebook as they are in face-to-face contacts?

A team of researchers headed by Dr. Andrew High at the University of Iowa recently investigated this question and published their findings in the article "Misery rarely gets company: The influence of emotional bandwidth on supportive communication on Facebook". The researchers created three distinct Facebook profiles of a fictitious person named Sara Thomas who had just experienced a break-up. The three profiles were identical in all respects except for how much information was conveyed about the recent (fictitious) break-up. In their article, High and colleagues use the expression "emotional bandwidth" to describe the extent of emotions conveyed in the Facebook profile.
In the low bandwidth scenario, the profile contained the following status update:

"sad and depressed:("

The medium bandwidth profile included a change in relationship status to "single" in the timeline, in addition to the  low bandwidth profile update "sad and depressed:(".

Finally, the high emotional bandwidth profile not only contained the updates of the low and medium bandwidth profiles, but also included a picture of a crying woman (the other two profiles had no photo, just the standard Facebook shadow image).

The researchers then surveyed 84 undergraduate students (enrolled in communications courses, average age 20, 53% female) and presented them with screenshots of one of the three profiles.


They asked the students to imagine that the person in the profile was a member of their Facebook network. After reviewing the assigned profile, each student completed a questionnaire asking about their willingness to provide support for Sara Thomas using a 9-point scale (1 = strongly disagree; 9 = strongly agree). The survey contained questions that evaluated the willingness to provide emotional support (e.g.  "Express sorrow or regret for her situation") and network support (e.g. "Connect her with people whom she may turn to for help''). In addition to being queried about their willingness to provide distinct forms of support, the students were also asked about their sense of community engendered by Facebook (e.g., "Facebook makes me feel I am a part of a community'') and their preference for online interactions over face-to-face interactions  (e.g., "I prefer communicating with other people online rather than face-to-face'').

High and colleagues hypothesized that the high emotional bandwidth profiles would elicit greater support from the students. In face-to-face interactions, it is quite common for us to provide greater support to a person – friend or stranger – if we see them overtly crying and therefore the researchers' hypothesis was quite reasonable. To their surprise, the researchers found the opposite. The willingness to provide emotional or network support was significantly lower among students who viewed the high emotional bandwidth profile! For example, average emotional support scores were 7.8 among students who saw Sara entering the "sad and depressed:(" update (low bandwidth) but the scores were only 6.5 among students who also saw the image of Sara crying and updating her relationship status to single (high bandwidth). Interestingly, students who preferred online interactions over face-to-face interactions or those who felt that Facebook created a strong sense of community responded positively to the high bandwidth profile.

There are some important limitations of the study. The students were asked to evaluate whether they would provide support to a fictitious person by imagining that she was part of their Facebook friends network. This is a rather artificial situation because actual supportive Facebook interactions occur among people who know each other. It is not easy to envision support for a fictitious person whose profile one sees for the first time. Furthermore, "emotional bandwidth" is a broad concept and it is difficult to draw general conclusions about "emotional bandwidth" from the limited differences between the three profiles. Increasing the sample size of the study subjects as well as creating a broader continuum of emotional bandwidth differences (e.g. including profiles which include pictures of a fictitious Sara Thomas who is not crying, using other status updates, etc.), and also considering scenarios that are not just related to break-ups (e.g. creating profiles of a fictitious grieving person who has lost a loved one) would be useful for an in-depth analysis of "emotional bandwidth".

The study by High and colleagues is an intriguing and important foray into the cyberpsychology of emotional self-disclosure and supportive communication on Facebook. This study raises important questions about how cyberbehavior differs from real world face-to-face behavior, and the even more interesting question of why these behaviors are different. Online interactions omit the dynamic gestures, nuanced intonations and other cues which play a critical role in determining our face-to-face behavior. When we share emotions via Facebook, our communication partners are often spatially and temporally displaced. This allows us to carefully "edit" what we disclose about ourselves, but it also allows our audience to edit their responses, unlike the comparatively spontaneous responses of a person sitting next to us. Facebook invites us to use the "Share" button, but we need to remember that online "sharing" is a sharing between heavily edited and crafted selves that is very different from traditional forms of "sharing".     

********************************

Acknowledgments: An earlier version of this article was first published at 3Quarksdaily. The images from the study profiles were provided by Dr. Andrew High, copyright of the images - Dr. Andrew High. 

Reference: Misery rarely gets company: The influence of emotional bandwidth on supportive communication on Facebook, AC High, A Oeldorf-Hirsch, S Bellur, Computers in Human Behavior (2014) 34, 79-88





High, A., Oeldorf-Hirsch, A., & Bellur, S. (2014). Misery rarely gets company: The influence of emotional bandwidth on supportive communication on Facebook Computers in Human Behavior, 34, 79-88 DOI: 10.1016/j.chb.2014.01.037

Should Doctors ‘Google’ Their Patients?

Beware of what you share. Employers now routinely utilize internet search engines or social network searches to obtain information about job applicants. A survey of 2,184 hiring managers and human resource professionals conducted by the online employment website CareerBuilder.com revealed that 39% use social networking sites to research job candidates. Of the group who used social networks to evaluate job applicants, 43% found content on a social networking site that caused them to not hire a candidate, whereas only 19% found information that that has caused them to hire a candidate.

The top reasons for rejecting a candidate based on information gleaned from social networking sites were provocative or inappropriate photos/information, including information about the job applicants' history of substance abuse. This should not come as a surprise to job applicants in the US. After all, it is not uncommon for employers to invade the privacy of job applicants by conducting extensive background searches, ranging from the applicant's employment history and credit rating to checking up on any history of lawsuits or run-ins with law enforcement agencies. Some employers also require drug testing of job applicants. The internet and social networking websites merely offer employers an additional array of tools to scrutinize their applicants. But how do we feel about digital sleuthing when it comes to relationship that is very different than the employer-applicant relationship – one which is characterized by profound trust, intimacy and respect, such as the relationship between healthcare providers and their patients?


The Hastings Center Report is a peer-reviewed academic bioethics journal which discusses the ethics of "Googling a Patient" in its most recent issue. It first describes a specific case of a twenty-six year old patient who sees a surgeon and requests a prophylactic mastectomy of both breasts. She says that she does not have breast cancer yet, but that her family is at very high risk for cancer. Her mother, sister, aunts, and a cousin have all had breast cancer; a teenage cousin had ovarian cancer at the age of nineteen; and that her brother was treated for esophageal cancer at the age of fifteen. She also says that she herself has suffered from a form of skin cancer (melanoma) at the age of twenty-five and that she wants to undergo the removal of her breasts without further workup because she wants to avoid developing breast cancer. She says that her prior mammogram had already shown abnormalities and she had been told by another surgeon that she needed the mastectomy.

Such prophylactic mastectomies, i.e. removal of both breasts, are indeed performed if young women are considered to be at very high risk for breast cancer based on their genetic profile and family history. The patient's family history – her mother, sister and aunts being diagnosed with breast cancer – are indicative of a very high risk, but other aspects of the history such as her brother developing esophageal cancer at the age of fifteen are rather unusual. The surgeon confers with the patient's primary care physician prior to performing the mastectomy and is puzzled by the fact that the primary care physician cannot confirm many of the claims made by the patient regarding her prior medical history or her family history. The physicians find no evidence of the patient ever having been diagnosed with a melanoma and they also cannot find documentation of the prior workup. The surgeon then asks a genetic counselor to meet with the patient and help resolve the discrepancies. During the evaluation process, the genetic counselor decides to ‘google' the patient.


The genetic counselor finds two Facebook pages that are linked to the patient. One page appears to be a personal profile of the patient, stating that in addition to battling stage four melanoma (a very advanced stage of skin cancer with very low survival rates), she has recently been diagnosed with breast cancer. She also provides a link to a website soliciting donations to attend a summit for young cancer patients. The other Facebook page shows multiple pictures of the patient with a bald head, suggesting that she is undergoing chemotherapy, which is obviously not true according to what the genetic counselor and the surgeon have observed. Once this information is forwarded to the surgeon, he decides to cancel the planned surgery. It is not clear why the patient was intent on having the mastectomy and what she would gain from it, but the obtained information from the Facebook pages and the previously noted discrepancies are reason enough for the surgeon to rebuff the patient's request for the surgery.

Two groups of biomedical ethics experts then weigh in on the case and the broader question of whether or not health care professionals should ‘google' patients. The first group of ethics experts feels that uninvited patient ‘googling' is generally a bad practice for three main reasons:

1. It allows healthcare professionals to withdraw from their patients and start relying on online data and information gleaned from social networking sites instead of interacting with the patient and addressing the key issues head-on.
2. The ‘googling' of patients erodes the trust between the healthcare professional and the patient. Patients might feel a sense of betrayal that the healthcare professional "spied" on them.
3. An internet search or review or social network pages linked to the patient represents an invasion of the privacy of the patient. The patient should have the right to decide what information to disclose and what not to disclose, but by surreptitiously obtaining this information, the healthcare provide circumvents the right to privacy of the patient.

A separate panel of reviewers arrives at a very different conclusion and specifically points to this case as an example where it was imperative to ‘google' the patient. As this panel points out, the genetic counselor used a legal method to search the internet and found information on public Facebook profiles after having found many red flags and inconsistencies in the patient's medical history. By finding the information on Facebook, the surgeon and the counselor were able to prevent a self-injurious, deceptive and possibly fraudulent scheme of the patient to go forward. This panel of experts goes as far as saying that it would have actually been irresponsible to not perform the Google search after all the red flags and inconsistencies were identified.
As with all ethical dilemmas, it is difficult to find the correct answer. The first panel brings up good points that the relationship between a healthcare professional and a patient is characterized by trust and respect of privacy, but I tend to agree with the second panel in the case of this patient. It illustrates that the ‘googling' was able to avert an unnecessary and irreversible surgery. This was not just an indiscriminate ‘googling' or searching of private information on Facebook pages. The action was prompted by very real concerns about contradictory information regarding the patient's medical history. On balance, the benefit of avoiding the unnecessary surgery probably outweighed the risk of harming the trust between the healthcare professional and the patient – one which was already undermined by the patient's deception.

This case is rather unusual because it is probably quite rare that a surgeon or a genetic counselor would find valuable information on a patient by merely searching Google or Facebook for information. The type of information that could be of value to most healthcare providers is not usually disclosed on public sites or social network pages. For example, a cardiologist may be interested in finding out why a patient's cholesterol levels are not decreasing despite being placed on optimal medications and being advised to cut down the dietary intake of cholesterol. The cardiologist may suspect that the patient is not really taking the medications or perhaps eating much more dietary cholesterol than the patient is willing to disclose during the doctor's visits. However, it is unlikely that the patient's Facebook page will chronicle whether or not the patient secretly eats cheese omelets on a daily basis or chooses not to take his cholesterol medications.

On the other hand, other healthcare professionals could find important diagnostic clues when reviewing the Facebook page of a patient. Psychiatrists or psychologists may be able to get a much better sense of a patient's mental health and functioning by reviewing the daily posts and interactions of a patient with friends and family members instead of just having to rely on the brief snapshot when they interview the patient during a 30 minute visit.

The study ""To Google or not to Google: Graduate students' use of the Internet to access personal information about clients." by the psychologists DeLillo and Gale surveyed 854 students enrolled in clinical, counseling, and school psychology doctoral programs in the United States and Canada, asking them how they felt about using Google or social networking websites to learn more about their clients/patients. Interestingly, two-thirds of the psychologists-in-training felt that it was never acceptable or usually not acceptable to use web search engines in order to find additional information about their clients. This feeling was even more pronounced when it came to social networking sites: 76.8% of the students thought that this was never acceptable or usually not acceptable.

However, despite these feelings, 97.8% of the students had searched for at least one client's information using search engines such as Google, whereas 94.4% had searched for at least one client's information using social networking websites. Importantly, 76.8% of the therapists who had conducted the searches for client information on social networking sites also reported that it was either always or usually unacceptable! This suggests a significant dissonance between the ethical perception of the therapists and their actions. Furthermore, more than 80% of the therapists who had conducted the searches said that their clients were aware of the internet and social networking searches they were conducting.

The case study with the patient requesting the mastectomy and the high prevalence of using the internet to perform searches on patients/clients by psychologists highlights the ethical dilemmas that are emerging in our culture of digital sharedom. The internet with its often very public display of individual information may be a powerful tool for certain healthcare professionals, but we also need to develop ethical guidelines for how healthcare professionals should use this tool. For medical procedures and tests, healthcare professionals have to obtain informed consent from their patients, discussing the risks and benefits of the procedure or test. Should healthcare professionals also obtain informed consent from patients before they pry into their social media networks? Or would that defeat the purpose because the patients might change the privacy settings or change the content of their posts, knowing that healthcare professionals might be reviewing them? Should healthcare professionals in specialties such as psychology and psychiatry ‘google' all their patients – just like they now ask questions about substance abuse to all patients – or only if there are certain red flags?

The survey of psychologists-in-training highlights the cognitive dissonance that healthcare professionals may experience: They may reject such searches on their clients or patients in the abstract, but they may still choose to perform the searches, probably because they think it will allow them to provide better care for their clients and patient. Instead of relying of idiosyncratic decisions made by professionals, we have to establish the ethical ground-rules for how healthcare professionals can use search engines or social networking sites when obtaining information about individuals. We may have become so accustomed to invasions of our privacy by government agencies and corporations that we sometimes forget that privacy is instrumental in maintaining our individuality. Especially in relationships that are founded on an extraordinary degree of trust, such as those between healthcare professionals and their patients or clients, we need to ensure that this trust is not eroded by the dark side of sharedom.

Acknowledgements: I would like to thank Ryan Hunt from CareerBuilder for clarifying the survey results. An earlier version of this article was first published on  the 3Quarksdaily blog.

References:

1. Rebecca Volpe, George Blackall, and Michael Green; and Danny George, Maria Baker, and Gordon Kauffman, "Googling a Patient" Hastings Center Report 43, no. 5 (2013): 14-15.
2. DiLillo, David; Gale, Emily B. "To Google or not to Google: Graduate students' use of the Internet to access personal information about clients."Training and Education in Professional Psychology, Vol 5(3), Aug 2011, 160-166. doi: 10.1037/a0024441

Volpe R, Blackall G, & Green M (2013). Case study. Googling a patient. Commentary. The Hastings Center report, 43 (5), 14-5 PMID: 24092585





  DiLillo, D., & Gale, E. (2011). To Google or not to Google: Graduate students' use of the Internet to access personal information about clients. Training and Education in Professional Psychology, 5 (3), 160-166 DOI: 10.1037/a0024441

Scientism Reloaded

The "Reclaim Scientism" movement is gaining momentum. In his recent book "The Atheist's Guide to Reality: Enjoying Life without Illusions", the American philosopher Alexander Rosenberg suggests that instead of viewing the word "scientism" as an epithet, atheists should expropriate it and use it as a positive term which describes their worldview. Rosenberg also provides a descriptive explanation of how the term "scientism" is currently used:

Scientism — noun; scientistic — adjective.
Scientism has two related meanings, both of them pejorative. According to one of these meanings, scientism names the improper or mistaken application of scientific methods or findings outside their appropriate domain, especially to questions treated by the humanities. The second meaning is more common: Scientism is the exaggerated confidence in the methods of science as the most (or the only) reliable tools of inquiry, and an equally unfounded belief that at least the most well established of its findings are the only objective truths there are.

Rosenberg's explanation of "scientism" is helpful because it highlights the difference between science and scientism. Science refers to applying scientific methods as tools of inquiry to collect and interpret data, whereas "scientism" refers to cultural and ideological views promoting the primacy or superiority of scientific methods over all other tools of inquiry.  Some scientists embrace scientistic views, in part because scientism provides a much-needed counterbalance to aggressive anti-science attitudes that are prevalent on both ends of the political spectrum and among some religious institutions. However, other scientists are concerned about propping up scientism as a bulwark against ideological science-bashing because it smacks of throwing out the baby with the bathwater. Science is characterized by healthy skepticism, the dismantling of dogmatic views and a continuous process of introspection and self-criticism. Infusing science with ideological stances concerning the primacy of the scientific method could undermine the power of science which is rooted in its willingness to oppose ideological posturing.

As a scientist who investigates signaling mechanisms and the metabolic activity of stem cells, I am concerned about the rise of some movements that fall under the "scientism" umbrella, because they have the possibility to impede scientific discovery. Scientific progress relies on recognizing the limitations and flaws in existing scientific concepts and refuting scientific views that cannot be adequately explained by newer scientific observations. An exaggerated confidence in the validity of scientific findings could stifle such refutations. For example, some of the most widely cited scientific papers in the field of stem cell biology cannot be replicated, but they have had an enormous detrimental impact on the science and medicine, in part because of an exaggerated faith in the validity of some initial experiments.


I first began studying the use of stem and progenitor cells to enhance cardiovascular repair and regeneration over a decade ago. At that time, many of my colleagues and I were excited about a recent paper published by a group of scientists based at New York Medical College in the high-profile scientific journal Nature in 2001. The paper suggested that injected adult bone marrow stem cells could be successfully converted into functional heart cells and recover heart function after a heart attack by generating new heart tissue. The usage of adult regenerative cells was a very attractive option because it would allow patients to be treated with their own cells and could circumvent the ethical and political controversies associated with embryonic stem cells. This animal study gained even more traction when supportive experimental and human studies were published by other scientists. Then a German research group under the direction of the cardiologist Bodo Strauer published a paper in 2002 which showed that not only could adult human bone marrow cells be safely injected into heart attack patients but that these adult cells  even appeared to improve  heart function.

The stir caused by these discoveries was not just confined to scientists. The findings were widely reported in the media and I recall numerous discussions with physicians who claimed that cardiovascular disease would soon be a problem of the past, because patients would receive routine bone marrow injections after heart attacks. One colleague even advised me to reconsider my career choices since the usage of bone marrow cells could address most if not all issues in cardiovascular regeneration.

This excitement was somewhat dampened when a refutation of the 2001 Nature paper was published in 2004, also in the journal Nature. A collaborative effort of two US-based stem cell research groups was not able to replicate the findings of the 2001 paper. The scientists were unable to find any significant conversion of adult bone marrow cells into functional heart cells. However, many physicians, scientists and patients had already adopted an unshakable belief in the validity of the bone marrow cell treatments after heart attacks. Hundreds of heart attack patients were being enrolled in clinical trials involving the injection of bone marrow cells. Clinics in Thailand or Mexico began offering bone marrow injections to heart patients from all around the world– for a hefty price, both in terms of monetary payments and in terms of safety because they exposed patients to the risks of invasive injections of bone marrow cells into their hearts.

Despite the fact that the initial clinical studies with small numbers of enrolled patients had shown a beneficial effect of bone marrow cell injections, subsequent trials could not confirm these early successes. It became apparent that even if bone marrow cell injections did exert a therapeutic benefit in heart attack patients, these benefits were rather modest. Scientists increasingly realized that the observed benefits may have been causally unrelated to the small fraction of stem cells contained within the bone marrow. Instead of bone marrow stem cells becoming functional heart cells, some bone marrow cells may have merely released protective proteins which could explain the slight improvement in heart function, without necessarily generating new heart tissue. One of the largest bone marrow cell treatment trials for heart attack patients to date was just recently published in 2013 and showed no evidence of improved heart function following the cell injections.  

In hindsight, many of us have wondered why we were not more skeptical of the initial findings. When compared to embryonic stem cells, adult bone marrow stem cells have a very limited ability to differentiate into cell types other than those typically found in the bone marrow. Furthermore, the clinical studies which reported successful treatment of heart attack patients used unpurified bone marrow cells from the patients. The stem cell content of such unpurified preparations is roughly 1% or less, which means that 99% of the injected bone marrow cells were NOT stem cells. For the tiny fraction of bona fide stem cells in the bone marrow to convert into sufficient numbers of beating heart cells and even create new functional heart tissue would have been akin to a miracle.

Critical thinking and healthy skepticism, the scientific peer review processor and even common sense should have alerted us to the problems associated with these claims, but they all failed. Perhaps scientists, physicians and patients were so excited by the prospect of creating new heart tissue that they suspended much-needed skepticism. Exaggerated confidence in the validity of the scientific data published in highly regarded scientific journals may have played an important role. Unintentional cognitive biases of scientists who conducted the experiments and a disregard for alternative explanations could have also contributed to the propagation of ideas that would withstand subsequent testing. Scientific misconduct may also play a role. For example, the cardiologist who conducted the first clinical studies with bone marrow cell infusions in heart attack patients was investigated by his university for scientific misconduct because a review of his work had identified massive errors.

This is just one example to illustrate problems associated with an exaggerated confidence in the validity of scientific findings, a kind of confidence which scientism engenders. Such examples are by no means restricted to stem cell biology. A recent analysis of scientific reproducibility in cancer research claimed that only 11% of published cancer biology papers could be independently validated, and other areas of scientific research may be similarly afflicted by the problem of irreproducibility of published, peer-reviewed scientific papers.
Increasing numbers of scientists are recognizing that current approaches to interpreting and publishing scientific data are severely flawed. Exaggerated confidence in the validity of scientific findings is frequently misplaced and claims that scientific results represent objective truths need to be re-evaluated particularly when a high percentage of experimental results cannot be replicated by fellow scientists. In this particular context, the views of scientists who are trying to learn lessons from the failures of the scientific peer review process are not so different from those of "scientism" critics. However, many scientists, myself included, remain reluctant to use the expression "scientism".  

Rosenberg illustrates the problems associated with the word "scientism". Since "scientism" is often used as an epithet, invoking "scientism" may impede constructive discussions about the appropriateness of applying scientific methods. While a question such as "Can issues of morality be answered by scientific experiments?" may be important, introducing the term "scientism" with all its baggage distracts from addressing the question in a rational manner.
The other major issue associated with the term "scientism" is its vagueness. It is difficult to discuss "scientism" if it encompasses a broad range of distinct concepts such as the notion that science has to remain within certain boundaries as well as a criticism of overweening confidence in the validity of scientific findings. I can easily identify with asking for a realistic reappraisal of whether or not scientific results obtained by one laboratory constitute an objective, scientific truth but I am opposed to creating boundary lines that forbid certain forms of scientific inquiry because it might infringe on the domains of the humanities. Instead of the diffuse expression "scientism", I prefer the term "science mystique" to criticize the exaggerated, near-mythical confidence in the infallibility of scientific results. 

Rosenberg's view that the expression "scientism" and also the culture of "scientism" should be embraced received a big boost when the scientist Steven Pinker published his polemic essay "Science Is Not Your Enemy: An impassioned plea to neglected novelists, embattled professors, and tenure-less historians". Like Rosenberg, Pinker wants to rehabilitate the expression "scientism" and use it to indicate a positive, science-affirming worldview. Unfortunately, instead of engaging in a constructive dialogue about the culture of "scientism", Pinker reveals his condescending attitude towards the humanities throughout the essay. His notion of respect for the humanities consists of pointing out how much better off classical philosophers might have been if they had been aware of modern neuroscience. 

But Pinker does not comment on the converse proposition: Would scientists be better off if they knew more about philosophy? Pinker goes on to portray scientists as dynamic forward thinkers, while humanities scholars are supposedly weighed down by their intellectual inertia:

"Several university presidents and provosts have lamented to me that when a scientist comes into their office, it's to announce some exciting new research opportunity and demand the resources to pursue it. When a humanities scholar drops by, it's to plead for respect for the way things have always been done."

Pinker glosses over the reproducibility issues in science and reaffirms his faith in the current system of scientific peer review without commenting on the limitations of scientific peer review:

"Scientism, in this good sense, is not the belief that members of the occupational guild called "science" are particularly wise or noble. On the contrary, the defining practices of science, including open debate, peer review, and double-blind methods, are explicitly designed to circumvent the errors and sins to which scientists, being human, are vulnerable."

The philosopher and scientist Massimo Pigliucci wrote an excellent response to Steven Pinker, discussing the flaws inherent in Pinker's polemic and explaining why promoting a culture of scientism or a "science mystique" is not in the interest of science. I also agree with the physicist Sean Carroll who reminds us that we should get rid of the term "scientism"; not because he wants to get rid of a critical evaluation of science, but because he thinks this poorly defined term is not very helpful.

Whether or not we use the word "scientism", it is apparent that the debates between the critics and defenders of the culture of "scientism" are here to stay. It is unlikely that rehabilitating the unhelpful word "scientism" or polemical stances towards the humanities will contribute to this debate in a meaningful manner. The challenge for scientists and non-scientists is to embrace and address the legitimate criticisms of science without promoting the agenda of irrational anti-science bashing. 



Note: An earlier version of this article was first published on the 3Quarksdaily blog

There Was No Couch: On Mental Illness and Creativity

The psychiatrist held the door open for me and my first thought as I entered the room was “Where is the couch?”. Instead of the expected leather couch, I saw a patient lying down on a flat operation table surrounded by monitors, devices, electrodes, and a team of physicians and nurses. The psychiatrist had asked me if I wanted to join him during an “ECT” for a patient with severe depression. It was the first day of my psychiatry rotation at the VA (Veterans Affairs Medical Center) in San Diego, and as a German medical student I was not yet used to the acronymophilia of American physicians. I nodded without admitting that I had no clue what “ECT” stood for, hoping that it would become apparent once I sat down with the psychiatrist and the depressed patient.

I had big expectations for this clinical rotation.  German medical schools allow students to perform their clinical rotations during their final year at academic medical centers overseas, and I had been fortunate enough to arrange for a psychiatry rotation in San Diego. The University of California (UCSD) and the VA in San Diego were known for their excellent psychiatry program and there was the added bonus of living in San Diego. Prior to this rotation in 1995, most of my exposure to psychiatry had taken the form of medical school lectures, theoretical textbook knowledge and rather limited exposure to actual psychiatric patients. This may have been part of the reason why I had a rather naïve and romanticized view of psychiatry. I thought that the mental anguish of psychiatric patients would foster their creativity and that they were somehow plunging from one existentialist crisis into another. I was hoping to engage in some witty repartee with the creative patients and that I would learn from their philosophical insights about the actual meaning of life. I imagined that interactions with psychiatric patients would be similar to those that I had seen in Woody Allen’s movies: a neurotic, but intelligent artist or author would be sitting on a leather couch and sharing his dreams and anxieties with his psychiatrist.

I quietly stood in a corner of the ECT room, eavesdropping on the conversations between the psychiatrist, the patient and the other physicians in the room. I gradually began to understand that that “ECT” stood for “Electroconvulsive Therapy”. The patient had severe depression and had failed to respond to multiple antidepressant medications. He would now receive ECT, what was commonly known as electroshock therapy, a measure that was reserved for only very severe cases of refractory mental illness. After the patient was sedated, the psychiatrist initiated the electrical charge that induced a small seizure in the patient. I watched the arms and legs of the patients jerk and shake. Instead of participating in a Woody-Allen-style discussion with a patient, I had ended up in a scene reminiscent of “One Flew Over the Cuckoo's Nest”, a silent witness to a method that I thought was both antiquated and barbaric. The ECT procedure did not take very long, and we left the room to let the sedation wear off and give the patient some time to rest and recover. As I walked away from the room, I realized that my ridiculously glamorized image of mental illness was already beginning to fall apart on the first day of my rotation. 

During the subsequent weeks, I received an eye-opening crash course in psychiatry. I became acquainted with DSM-IV, the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders which was the sacred scripture of American psychiatry according to which mental illnesses were diagnosed and classified. I learned ECT was reserved for the most severe cases, and that a typical patient was usually prescribed medications such as anti-psychotics, mood stabilizers or anti-depressants. I was surprised to see that psychoanalysis had gone out of fashion. Depictions of the USA in German popular culture and Hollywood movies had led me to believe that many, if not most, Americans had their own personal psychoanalysts. My psychiatry rotation at the VA took place in the mid 1990s, the boom time for psychoactive medications such as Prozac and the concomitant demise of psychoanalysis.

I found it exceedingly difficult to work with the DSM-IV and to appropriately diagnose patients. The two biggest obstacles I encountered were a) determining cause –effect relationships in mental illness and b) distinguishing between regular human emotions and true mental illness. The DSM-IV criteria for diagnosing a “Major Depressive Episode”, included depressive symptoms such as sadness or guilt which were severe enough to “cause clinically significant distress or impairment in social, occupational, or other important areas of functioning”. I had seen a number of patients who were very sad and had lost their job, but I could not determine whether the sadness had impaired their “occupational functioning” or whether they had first lost their job and this had in turn caused profound sadness. Any determination of causality was based on the self-report of patients, and their memories of event sequences were highly subjective.

The distinction between “regular” human emotions and mental illness was another challenge for me and the criteria in the DSM-IV manual seemed so broad that what I would have considered “sadness” was now being labeled as a Major Depression. A number of patients that I saw had severe mental illnesses such as depression, a condition so disabling that they could hardly eat, sleep or work. The patient who had undergone ECT on my first day belonged to that category. However, the majority of patients exhibited only some impairment in their sleep or eating patterns and experienced a degree of sadness or anxiety that I had seen in myself or my friends. I had considered transient episodes of anxiety or unhappiness as part of the spectrum of human emotional experience. The problem I saw with the patients in my psychiatry rotation was these patients were not only being labeled with a diagnosis such as “Major Depression”, but were then prescribed antidepressant medications without any clear plan to ever take them off the medications. By coincidence, that year I met the forensic psychiatrist Ansar Haroun, who was also on faculty at UCSD and was able to help me with my concerns. Due to his extensive work in the court system and his rigorous analysis of mental states for legal proceedings, Haroun was an expert on causality in psychiatry as well the definition of what constitutes a truly pathological mental state.

Regarding the issue of causality, Haroun explained to me the complexity of the mind and mental states makes it extremely difficult to clearly define cause and effect relationships in psychiatry. In infectious diseases, for example, specific bacteria can be identified by laboratory tests as causes of a fever. The fever normally does not precede the bacterial infection nor does it cause the bacterial infection.  The diagnosis of mental illnesses, on the other hand, rests on subjective assessments of patients and is further complicated by the fact that there are no clearly defined biological causes or even objective markers of most mental illnesses. Psychiatric diagnoses are therefore often based on patterns of symptoms and a presumed causality. If a patient exhibits symptoms of a depressed mood and has also lost his or her job during that same time period, psychiatrists then have to diagnose whether the depression was the cause of losing the job or whether the job loss caused depressive symptoms. In my limited experience with psychiatry and the many discussions I have had with practicing psychiatrists, it appears that the leeway given to psychiatrists to assess cause-effect relationships may result in an over-diagnosis of mental illnesses or an over-estimation of their impact.

I also learnt from Haroun that the question of how to address the distinction between the spectrum of “regular” human emotions and actual mental illness had resulted in a very active debate in the field of psychiatry. Haroun directed me towards the writings of Tom Szasz, who was a brilliant psychiatrist but also a critic of psychiatry, repeatedly pointing out the limited scientific evidence for diagnoses of mental illness.  Szasz’ book “The Myth of Mental Illness” was first published in 1960 and challenged the foundations of modern psychiatry. One of his core criticisms of psychiatry was that his colleagues had begun to over-diagnose mental illnesses by blurring the boundaries between everyday emotions and true diseases. Every dis-ease (discomfort) was being turned into a disease that required a therapy. The reasons for this overreach by psychiatry were manifold, ranging from society and the state trying to regulate what was acceptable or normal behavior to psychiatrists and pharmaceutical companies that would benefit financially from the over-diagnosis of mental illness. An excellent overview of his essays can be found in his book “The Medicalization of Everyday Life”. Even though Tom Szasz passed away earlier this year, psychiatrists and researchers are now increasingly voicing their concerns about the direction that modern psychiatry has taken. Allan Horwitz and Jerome Wakefield, for example, have recently published “The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder” and “All We Have to Fear: Psychiatry's Transformation of Natural Anxieties into Mental Disorders”. Unlike Szasz who even went as far as denying the existence of mental illness, Horowitz and Wakefield have taken a more nuanced approach. They accept the existence of true mental illnesses, admit these illnesses can be disabling and acknowledge the patients who are afflicted by mental illnesses do require psychiatric treatment. However, Horowitz and Wakefield criticize the massive over-diagnosis of mental illness and point out the need to distinguish true mental illnesses from normal sadness and anxiety.


Before I started my psychiatry rotation in San Diego, I had been convinced that mental illness fostered creativity. I had never really studied the question in much detail, but there were constant references in popular culture, movies, books and TV shows to the creative minds of patients with mental illness. The supposed link between mental illness and creativity was so engrained in my mind that the word “psychotic” automatically evoked images of van Gogh’s paintings and other geniuses whose creative minds were fueled by the bizarreness of their thoughts. Once I began seeing psychiatric patients who truly suffered from severe disabling mental illnesses, it became very difficult for me to maintain this romanticized view of mental illness. People who truly suffered from severe depression had difficulties even getting out of bed, getting dressed and meeting their basic needs. It was difficult to envision someone suffering from such a disabling condition to be able to write large volumes of poetry or to analyze the data from ground-breaking experiments. The brilliant book “Creativity and Madness: New Findings and Old Stereotypes” by Albert Rothenberg helped me understand that the supposed link between creativity and mental illness was primarily based on myths, anecdotes and a selection bias in which the creative accomplishments of patients with mental illness were glorified and attributed to the illness itself. Geniuses who suffered from schizophrenia or depression were not creative because of their mental illness but in spite of their mental illness.

I began to realize that the over-diagnosis of mental illness and the departure of causality that had become characteristic for contemporary psychiatry also helped foster the myth that mental illness enhances creativity. Many beautiful pieces of literature or art can be inspired by emotional states such as the sadness of unrequited love or the death of a loved one. Creativity is often a response to a state of discomfort or dis-ease, an attempt to seek out comfort. However, if definitions of mental illness are broadened to the extent that nearly every such dis-ease is considered a disease, one can easily fall into the trap of believing that mental illness indeed begets creativity. In respect to establishing causality, Rothenberg found, contrary to the prevailing myth, mental illness was actually a disabling condition that prevented creative minds from completing their artistic or scientific tasks. A few years ago, I came across “Poets on Prozac: Mental Illness, Treatment, and the Creative Process” a collection of essays written by poets who suffer from mental illness. The personal accounts of most poets suggest that their mental illnesses did not help them write their poetry, but actually acted as major hindrances. It was only when their illness was adequately treated and they were in a state of remission that they were able to write poems. A recent comprehensive analysis of studies that attempt to link creativity and mental illness can be found in the excellent textbook “Explaining Creativity: The Science of Human Innovation” by Keith Sawyer, who concludes that there is no scientific evidence for the claim that mental illness promotes creativity. He also points to a possible origin of this myth:

The mental illness myth is based in cultural conceptions of creativity that date from the Romantic era, as a pure expression of inner inspiration, an isolated genius, unconstrained by reason and convention.

I assumed that the myth had finally been laid to rest, but, to my surprise I came across the headline Creativity 'closely entwined with mental illness' on the BBC website in October 2012. The BBC story was referring to the large-scale Swedish study “Mental illness, suicide and creativity: 40-Year prospective total population study” by Simon Kyaga and his colleagues at the Karolinska Institute, published online in the Journal of Psychiatric Research. The BBC news report stated “Creativity is often part of a mental illness, with writers particularly susceptible, according to a study of more than a million people” and continued:

Lead researcher Dr Simon Kyaga said the findings suggested disorders should be viewed in a new light and that certain traits might be beneficial or desirable.
For example, the restrictive and intense interests of someone with autism and the manic drive of a person with bipolar disorder might provide the necessary focus and determination for genius and creativity.
Similarly, the disordered thoughts associated with schizophrenia might spark the all-important originality element of a masterpiece.

These statements went against nearly all the recent scientific literature on the supposed link between creativity and mental illness and once again rehashed the tired, romanticized myth of the mentally ill genius. I was puzzled by these claims and decided to read the original paper. There was the additional benefit of learning more about the mental health of Swedes, because my wife is a Swedish-American. It never hurts to know more about the mental health or the creative potential of one’s spouse.

Kyaga’s study did not measure creativity itself, but merely assessed correlations between self-reported “creative professions” and the diagnoses of mental illness in the Swedish population. Creative professions included scientific professions (primarily scientists and university faculty members) as well as artistic professions such as visual artists, authors, dancers and musicians. The deeply flawed assumption of the study was that if an individual has a “creative profession”, he or she has a higher likelihood of being a creative person. Accountants were used as a “control”, implying that being an accountant does not involve much creativity. This may hold true for Sweden, but the creativity of accountants in the USA has been demonstrated by the recent plethora of financial scandals. The size of the Kyaga study was quite impressive, involving over one million patients and collecting data on the relatives of patients. The fact that Sweden has a total population of about 9.5 million and that more than one million of its adult citizens are registered in a national database as having at least one mental illness is both remarkable and worrisome.
The main outcome was the likelihood that patients with certain mental illnesses such as depression, schizophrenia or anxiety disorders were engaged in a “creative profession”. The results of the study directly contradicted the BBC hyperbole:

We found no positive association between psychopathology and overall creative professions except for bipolar disorder. Rather, individuals holding creative professions had a significantly reduced likelihood of being diagnosed with schizophrenia, schizoaffective disorder, unipolar depression, anxiety disorders, alcohol abuse, drug abuse, autism, ADHD, or of committing suicide.

Not only did the authors fail to find a positive correlation between creative professions and mental illnesses (with the exception of bipolar disorder), they actually found the opposite of what they had suspected: Patients with mental illnesses were less likely to engage in a creative profession.
Their findings do not come as a surprise to anyone who has been following the scientific literature on this topic. After all, the disabling features of mental illness make it very difficult to maintain a creative profession. Kyaga and colleagues also presented a contrived subgroup analysis, to test whether there was any group within the “creative professions” that showed a positive correlation with mental illness. It appears contrived, because they only break down the artistic professions, but did not perform a similar analysis for the scientific professions. Among all these subgroup analyses, the researchers found a positive correlation between the self-reported profession ‘author’ and a number of mental illnesses. However, they also found that other artistic professions did not show such a positive correlation.

 How the results of this study gave rise to the blatant misinterpretation reported by the BBC that “the disordered thoughts associated with schizophrenia might spark the all-important originality element of a masterpiece” is a mystery in itself. It shows the power of the myth of the mad genius and how myths and convictions can tempt us to misinterpret data in a way that maintains the mythic narrative. The myth may also be an important component in the attempt to medicalize everyday emotions. The notion that mental illness fosters creativity could make the diagnosis more palatable. You may be mentally ill, but don’t worry, because it might inspire you to paint like van Gogh or write poems like Sylvia Plath.

A study of the prevalence of mental illness published in the Archives of General Psychiatry in 2005 estimated that roughly half of all Americans will have been diagnosed with a mental illness by time they reach the age of 75. This estimate was based on the DSM-IV criteria for mental illness, but the newer DSM-V manual will be released in 2013 and is likely to further expand the diagnosis of mental illness. The DSM-IV criteria had made allowance for bereavement to avoid diagnosing people who were profoundly sad after the loss of a loved one with the mental illness depression. This bereavement exemption will likely be removed from the new DSM-V criteria so that the diagnosis of major depression can be used even during the grieving period. The small group of patients who are afflicted with disabling mental illness do not find their suffering to be glamorous. There is a large number of patients who are experiencing normal sadness or anxiety and end up being inappropriately diagnosed with mental illness using broad and lax criteria of what constitutes an illness. Are these patients comforted by romanticized myths about mental illness? The continuing over-reach of psychiatry in its attempt to medicalize emotions, supported by the pharmaceutical industry that reaps large profits from this over-reach, should be of great concern to all of society. We need to wade through the fog of pseudoscience and myths to consider the difference between dis-ease and disease and the cost of medicalizing human emotions.



Image Credit: Wikimedia Commons Public Domain ECT machine (1960s) by Nasko and Self-Portait of van Gogh.

An earlier version of this article was first published on the 3Quarksdaily Blog.

Kyaga, S., Landén, M., Boman, M., Hultman, C., Långström, N., & Lichtenstein, P. (2013). Mental illness, suicide and creativity: 40-Year prospective total population study Journal of Psychiatric Research, 47 (1), 83-90 DOI: 10.1016/j.jpsychires.2012.09.010

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.

Composites

"Shorter sentences and simple words!" was the battle cry of all my English teachers. Their comments and corrections of our English-language essays and homework assignments were very predictable. Apparently, they had all sworn allegiance to the same secret Fraternal Order of Syntax Police. I am sure that students of the English language all over the world have heard similar advice from their teachers, but English teachers at German schools excel in their diligent use of linguistic guillotines to chop up sentences and words. The problem is that they have to teach English to students who think, write and breathe in German, the lego of languages.

Lego blocks invite the observer to grab them and build marvelously creative and complex structures. The German language similarly invites its users to construct composite words and composite sentences. A virtually unlimited number of composite nouns can be created in German, begetting new words which consist of two, three or more components with meanings that extend far beyond the sum of their parts. The famous composite German word "Schadenfreude" is now used worldwide to describe the shameful emotion of joy when observing harm befall others. It combines "Schaden" (harm or damage) and "Freude" (joy), and its allure lies in the honest labeling of a guilty pleasure and the inherent tension of combining two seemingly discordant words.

The lego-like qualities of German can also be easily applied to how sentences are structured. Commas are a German writer's best friends. A German sentence can contain numerous clauses and sub-clauses, weaving a quilt of truths, tangents and tangential truths, all combined into the serpentine splendor of a single sentence. Readers may not enjoy navigating their way through such verschachtelt sentences, but writers take great pleasure in envisioning a reader who unwraps a sentence as if opening a matryoshka doll only to find that the last word of a mammoth sentence negates its fore-shadowed meaning.


Even though our teachers indulged such playfulness when we wrote in German, they were all the more harsh when it came to our English assignments. They knew that we had a hankering for creating long sentences, so they returned them to us covered in red ink markings, indicative of their syntactic fervor. This obsession with short sentences and words took the joy out of writing in English. German was the language of beauty and poetry, whereas English became the language best suited for efficient communication. By the time I reached my teenage years, I began to lose interest in writing anything in English beyond our mandatory school assignments. I still enjoyed reading books in English, such as the books of Enid Blyton, but I could not fathom how a language of simple sentences and simple words could be used to create works of literary beauty. This false notion fell apart when I first read "Things Fall Apart" by Chinua Achebe.

The decision to read "Things Fall Apart" was not completely arbitrary. My earliest memories of this world are those of the years I spent as a child in Igboland. My family moved from Pakistan to Germany when I was one year old, but we soon moved on to Nigeria. Germany was financing the rehabilitation of the electrical power grid that had been destroyed during the Biafra War. My father was one of the electrical engineers sent from Germany to help with the restoration and expansion of the electrical power supply in the South-Eastern part of Nigeria – the region which was home to the Igbo people and which had attempted and failed to secede as the Republic of Biafra.

We first stayed in Enugu, the former capital of the transient Republic of Biafra and then lived in the city of Aba. My memories of the time in Igboland are just sequences of images and scenes, and it is difficult to make sense of all of them: Kind and friendly people, palm trees and mysterious forests, riding a tricycle in elliptical loops, visits to electrical sub-stations. We returned to Germany when I was four years old. I would never live in the Igboland again, but recalling the fragmented memories of those early childhood years has always evoked a sense of comfort and joy in me. When I came across "Things Fall Apart" as a fourteen-year old and learned that it took place in an Igbo village, I knew that I simply had to read it.

I was not prepared for the impact the book would have on me. Great books shake us up, change us in a profound and unpredictable manner, leaving footprints that are etched into the rinds of our soul. "Things Fall Apart" was the first great English language book that I read. I was mesmerized by its language. This book was living proof that one could write a profound and beautiful book in English, using short, simple sentences.

 As the Ibo say: "When the moon is shining the cripple becomes hungry for a walk."
And so Okonkwo was ruled by one passion— to hate everything that his father Unoka had loved. One of those things was gentleness and another was idleness.
 Living fire begets cold, impotent ash.
A child cannot pay for its mother's milk.

It wasn't just the beautiful language, aphorisms, Igbo proverbs and haunting images that made this book so unique. "Things Fall Apart" contained no heroes. The books that I had read before "Things Fall Apart" usually made it obvious who the hero was. But "Things Fall Apart" was different. Okonkwo was no hero, not even a tragic hero. But he also was no villain. As with so many of the characters in the book, I could see myself in them and yet I was also disgusted by some of the abhorrent acts they committed. I wanted to like Okonkwo, but I could not like a man who participated in the killing of his adopted son or nearly killed his wife in a fit of anger.

Guns fired the last salute and the cannon rent the sky. And then from the center of the delirious fury came a cry of agony and shouts of horror. It was as if a spell had been cast. All was silent. In the center of the crowd a boy lay in a pool of blood. It was the dead man's sixteen-year-old son, who with his brothers and half-brothers had been dancing the traditional farewell to their father. Okonkwo's gun had exploded and a piece of iron had pierced the boy's heart.

Achebe was not judging or mocking his characters, but sharing them with us. He was telling us about how real humans think and behave. As I read the book, I felt that I was being initiated into life. Life would be messy. Most of us would end up being neither true heroes nor true villains but composites of heroism and villainy.  If I did not want end up like Okwonkwo, the ultimate non-negotiator, I needed to accept the fact that my life would be a series of negotiations: negotiations between individuals, negotiations between conflicting identities and negotiations between values and cultures. The book described a specific clash of cultures in colonial Africa, but it was easy to apply the same clash to so many other cultures. I tried to envision Okwonkwo as an Indian farmer whose world began to fall apart when Arab armies invaded the Sindh. I imagined Okwonkwo as a Native American, a Roman or a Japanese warrior, each negotiating his way through cultural upheavals. The history of humankind is always that of things falling apart and, importantly, that of rebuilding after the falling apart.    

As soon as the day broke, a large crowd of men from Ezeudu's quarter stormed Okonkwo's compound, dressed in garbs of war. They set fire to his houses, demolished his red walls, killed his animals and destroyed his barn. It was the justice of the earth goddess, and they were merely her messengers. They had no hatred in their hearts against Okonkwo. His greatest friend, Obierika, was among them. They were merely cleansing the land which Okonkwo had polluted with the blood of a clansman.

I read "Things Fall Apart" to find my past, but it defined my future. It helped me recognize the beauty of the English language and prepared me for life in a way that no book had ever done before.

Notes: All quotes are from "Things Fall Apart" by Chinua Achebe

Image Credits: Stack of "Things Fall Apart" (by Scartol via Wikimedia Commons), Photo of a porcelain insulator with a bullet hole probably from the Biafra war, Photo taken from the Presidential Hotel in Enugu 1973.