quarta-feira, 5 de outubro de 2016

sexta-feira, 10 de julho de 2015

Science is heroic, with a tragic (statistical) flaw

https://www.sciencenews.org/blog/context/science-heroic-tragic-statistical-flaw

Science is heroic, with a tragic (statistical) flaw



Mindless use of statistical testing erodes confidence in research

statue of Achilles
Just as Achilles' heel was an unguarded weakness that ultimately brought down a hero of Greek mythology, dogmatic devotion to traditional statistical methods threatens public confidence in the institution of science.
SPONSOR MESSAGE
First of two parts
Science is heroic. It fuels the economy, it feeds the world, it fights disease. Sure, it enables some unsavory stuff as well — knowledge confers power for bad as well as good — but on the whole, science deserves credit for providing the foundation underlying modern civilization’s comforts and conveniences.
But for all its heroic accomplishments, science has a tragic flaw: It does not always live up to the image it has created of itself. Science supposedly stands for allegiance to reason, logical rigor and the search for truth free from the dogmas of authority. Yet science in practice is largely subservient to journal-editor authority, riddled with dogma and oblivious to the logical lapses in its primary method of investigation: statistical analysis of experimental data for testing hypotheses. As a result, scientific studies are not as reliable as they pretend to be. Dogmatic devotion to traditional statistical methods is an Achilles heel that science resists acknowledging, thereby endangering its hero status in society.
And that’s unfortunate. For science is still, in the long run, the superior strategy for establishing sound knowledge about nature. Over time, accumulating scientific evidence generally sorts out the sane from the inane. (In other words, climate science deniers and vaccine evaders aren’t justified by statistical snafus in individual studies.) Nevertheless, too many individual papers in peer-reviewed journals are no more reliable than public opinion polls before British elections.
Examples abound. Consider the widely reported finding that typographical ugliness improves test performance compared with questions printed in a nice normal font. It’s not true, as biological economist Terry Burnham has thoroughly established.
More emphatically, an analysis of 100 results published in psychology journals shows that most of them evaporated when the same study was conducted again, as a news report in the journal Nature recently recounted. And then there’s the fiasco about changing attitudes toward gay marriage, reported in a (now retracted) paper apparently based on fabricated data.
But fraud is not the most prominent problem. More often, innocent factors can conspire to make a scientific finding difficult to reproduce, as my colleague Tina Hesman Saey recently documented inScience News. And even apart from those practical problems, statistical shortcomings guarantee that many findings will turn out to be bogus. As I’ve mentioned on many occasions, the standard statistical methods for evaluating evidence are usually misused, almost always misinterpreted and are not very informative even when they are used and interpreted correctly.
Nobody in the scientific world has articulated these issues more insightfully than psychologist Gerd Gigerenzer of the Max Planck Institute for Human Development in Berlin. In a recent paper written with Julian Marewski of the University of Lausanne, Gigerenzer delves into some of the reasons for this lamentable situation.
Above else, their analysis suggests, the problems persist because the quest for “statistical significance” is mindless. “Determining significance has become a surrogate for good research,” Gigerenzer and Marewski write in the February issue of Journal of Management. Among multiple scientific communities, “statistical significance” has become an idol, worshiped as the path to truth. “Advocated as the only game in town, it is practiced in a compulsive, mechanical way — without judging whether it makes sense or not.”
Commonly, statistical significance is judged by computing a P value, the probability that the observed results (or results more extreme) would be obtained if no difference truly existed between the factors tested (such as a drug versus a placebo for treating a disease). But there are other approaches. Often researchers will compute confidence intervals — ranges much like the margin of error in public opinion polls. In some cases more sophisticated statistical testing may be applied. One school of statistical thought prefers the Bayesian approach, the standard method’s longtime rival.
Gigerenzer and Marewski emphasize that all these approaches have their pluses and minuses. Scientists should consider them as implements in a statistical toolbox — and should carefully think through which tool to use for a particular purpose.“Good science requires both statistical tools and informed judgment about what model to construct, what hypotheses to test, and what tools to use,” Gigerenzer and Marewski write.
Sadly, this sensible advice hasn’t penetrated a prejudice, born decades ago, that scientists should draw inferences from data via a universal mechanical method. The trouble is that no such single method exists, Gigerenzer and Marewski note. Therefore surrogates for this hypothetical ideal method have been adopted, primarily the calculation of P values. “This form of surrogate science fosters delusions and borderline cheating and has done much harm, creating … a flood of irreproducible results,” Gigerenzer and Marewski declare.
They trace the roots of the current conundrum to the “probabilistic revolution,” the subversion of faith in cause-and-effect Newtonian clockwork by the roulette wheels of statistical mechanics and quantum theory.
Ironically, the specter of statistical reasoning first surfaced in the social sciences. Among its early advocates was the 19th century Belgian astronomer-mathematician Adolphe Quetelet, who applied statistics to social issues such as crimes and birth and death rates. He noted regularities from year to year in murders and showed how analyses of populations could quantify the “average man” (l’homme moyen). Quetelet’s work inspired James Clerk Maxwell to apply statistical methods in analyzing the behavior of gas molecules. Soon many subrealms of physics adopted similar statistical methods.
For a while the statistical mindset invaded physics more thoroughly than in the social, medical and psychological sciences. “With few exceptions, social theorists hesitated to think of probability as more than an error term in the equation observation = true value + error,” Gigerenzer and Marewski write.
But then, beginning about 1940, statistics conquered the social sciences in the form of what Gigerenzer calls the “inference revolution.” Instead of using statistics to quantify measurement errors (a common use in other fields), social scientists began using statistics to draw inferences about a population from tests on a sample. “This was a stunning new emphasis,” Gigerenzer and Marewski write, “given that in most experiments, psychologists virtually never drew a random sample from a population or defined a population in the first place.” Most natural scientists regarded replication of the experiment as the key to establishing a result, while in the social sciences achieving statistical significance (once) became the prevailing motivation.
What emerged from the inference revolution was the “null ritual” — the practice of assuming a null hypothesis (no difference, or no correlation) and then rejecting it if the P value for observed data came out to less than 5 percent (P < .05). But that ritual stood on a shaky foundation. Textbooks invented the ritual by mashing up two mutually inconsistent theories of statistical inference, one devised by Ronald Fisher and the other by Jerzy Neyman and Egon Pearson.                                
“The inference revolution was not led by the leading scientists. It was spearheaded by humble nonstatisticians who composed statistical textbooks for education, psychology, and other fields and by the editors of journals who found in ‘significance’ a simple, ‘objective’ criterion for deciding whether or not to accept a manuscript,” Gigerenzer and Marewski write. “Inferential statistics have become surrogates for real replication.” And therefore many study “findings” fail when replication is attempted, if it is attempted at all.
Why don’t scientists do something about these problems? Contrary motivations! In one of the few popular books that grasp these statistical issues insightfully, physicist-turned-statistician Alex Reinhart points out that there are few rewards for scientists who resist the current statistical system.
“Unfortunate incentive structures … pressure scientists to rapidly publish small studies with slapdash statistical methods,” Reinhart writes in Statistics Done Wrong. “Promotions, tenure, raises, and job offers are all dependent on having a long list of publications in prestigious journals, so there is a strong incentive to publish promising results as soon as possible.”
And publishing papers requires playing the games refereed by journal editors.
“Journal editors attempt to judge which papers will have the greatest impact and interest and consequently those with the most surprising, controversial, or novel results,” Reinhart points out. “This is a recipe for truth inflation.”
Scientific publishing is therefore riddled with wrongness. It’s almost a miracle that so much truth actually does, eventually, leak out of this process. Fortunately there is enough of the good side of science to nurture those leaks enough so that by the standards of most of the world’s institutions, science still fares pretty damn well. But by its own standards, science fails miserably.
Follow me on Twitter: @tom_siegfried

Top 10 ways to save science from its statistical self

https://www.sciencenews.org/blog/context/top-10-ways-save-science-its-statistical-self

Top 10 ways to save science from its statistical self

Null hypothesis testing should be banished, estimating effect sizes should be emphasized

graph of p value
WORTHLESS  A P value is the probability of recording a result as large or more extreme than the observed data if there is in fact no real effect. P values are not a reliable measure of evidence.
SPONSOR MESSAGE
Second of two parts (read part 1)
Statistics is to science as steroids are to baseball. Addictive poison. But at least baseball has attempted to remedy the problem. Science remains mostly in denial.
True, not all uses of statistics in science are evil, just as steroids are sometimes appropriate medicines. But one particular use of statistics — testing null hypotheses — deserves the same fate with science as Pete Rose got with baseball. Banishment.
Numerous experts have identified statistical testing of null hypotheses — the staple of scientific methodology — as a prime culprit in rendering many research findings irreproducible and, perhaps more often than not, erroneous. Many factors contribute to this abysmal situation. In the life sciences, for instance, problems with biological agents and reference materials are a major source of irreproducible results, a new report in PLOS Biology shows. But troubles with “data analysis and reporting” are also cited. As statistician Victoria Stodden recently documented, a variety of statistical issues lead to irreproducibility. And many of those issues center on null hypothesis testing. Rather than furthering scientific knowledge, null hypothesis testing virtually guarantees frequent faulty conclusions.
“For more than half a century, distinguished scholars have published damning critiques of null hypothesis significance testing and have described the damage it does,” psychologist Geoff Cumming wrote last year in Psychological Science. “Very few defenses of null hypothesis significance testing have been attempted; it simply persists.”
A null hypothesis assumes that a factor being tested produces no effect (or an effect no different from some other factor). If experimental data are sufficiently unlikely (given the no-effect assumption), scientists reject the null hypothesis and infer that there is an effect. They call such a result “statistically significant.”
Statistical significance has nothing to do with actual significance, though. A statistically significant effect can be trivially small. Or even completely illusory.
Cumming, of the Statistical Cognition Laboratory at La Trobe University in Victoria, Australia, advocates a “new statistics” that dumps null hypothesis testing in favor of saner methods. “We need to make substantial changes to how we usually carry out research,” he declares. In his Psychological Science paper (as well as in a 2012 book), he describes an approach that focuses on three priorities: estimating the magnitude of an effect, quantifying the precision of that estimate, and combining results from multiple studies to make those estimates more precise and reliable.
Implementing Cumming’s new statistics will require more than just blog posts lamenting the problems. Someone needs to promote the recommendations that he and other worried researchers have identified. As in a Top 10 list. And since the situation is urgent, appended right here and now are my Top 10 ways to save science from its statistical self:

10. Ban P values

Statistical significance tests are commonly calculated using P values (the probability of observing the measured data — or data even more extreme — if the null hypothesis is correct). It has been repeatedly demonstrated that P values are essentially worthless as a measure of evidence. For one thing, different samples from the same dataset can yield dramatically different P values. “Any calculated value of P could easily have been very different had we merely taken a different sample, and therefore we should not trust any P value,” writes Cumming.
On occasion some journal editors have banned P values, most recently in Basic and Applied Social Psychology. Ideally there would be an act of Congress (and a United Nations resolution) condemning P values and relegating them to the same category as chemical weapons and smoking in airplanes.

9. Emphasize estimation

A major flaw with yes-or-no null hypothesis tests is that the right answer is almost always “no.” In other words, a null hypothesis is rarely true. Seldom would anything worth testing have an absolutely zero effect. With enough data, you can rule out virtually any null hypothesis, as psychologists John Kruschke and Torrin Liddell of Indiana University point out in a recent paper.
The important question is not whether there’s an effect, but how big the effect is. And null hypothesis testing doesn’t help with that. “The result of a hypothesis test reveals nothing about the magnitude of the effect or the uncertainty of its estimate, which are the key things we should want to know,” Kruschke and Liddell assert.
Cumming advocates using statistics to estimate actual effect magnitude in preference to null hypothesis testing, which “prompts us to see the world as black or white, and to formulate our research aims and make our conclusions in dichotomous terms — an effect … exists or it does not.”

8. Rethink confidence intervals

Estimating an effect’s magnitude isn’t enough — you need to know how precise that estimate is. Such precision is commonly expressed by a confidence interval, similar to an opinion poll’s margin of error. Confidence intervals are already often reported, but they are often not properly examined to infer an effect’s true importance. A result trumpeted as “statistically significant,” for instance, may have a confidence interval covering such a wide range that the actual effect size could be either tiny or titanic. And when a large confidence interval overlaps with zero effect, researchers typically conclude that thereis no effect, even though the confidence interval is so large that a sizable effect should not be ruled out.
“Researchers must be disabused of the false belief that if a finding is not significant, it is zero,” Kruschke and Liddell write. “This belief has probably done more than any of the other false beliefs about significance testing to retard the growth of cumulative knowledge in psychology.” And no doubt in other fields as well.
But properly calculated and interpreted, confidence intervals are useful measures of precision, Cumming writes. It’s just important that “we should not lapse back into dichotomous thinking by attaching any particular importance to whether a value of interest lies just inside or just outside our confidence interval.”

7. Improve meta-analyses

As Kruschke and Liddell note, each sample from a population will produce a different estimate of an effect. So no one study ever provides a thoroughly trustworthy result. “Therefore, we should combine the results of all comparable studies to derive a more stable estimate of the true underlying effect,” Kruschke and Liddell conclude. Combining studies in a “meta-analysis” is already common practice in many fields, such as biomedicine, but the conditions required for legitimate (and reliable) meta-analysis are seldom met. For one thing, it’s important to acquire results from every study on the issue, but many are unpublished and unavailable. (Studies that find a supposed effect are more likely to get published than those that don’t, biasing meta-analyses toward validating effects that aren’t really there.)
A meta-analysis of multiple studies can in principle sharpen the precision of an effect’s estimated size. But most meta-analyses typically create very large samples in order that small alleged effects can achieve statistical significance in a null hypothesis test. A better approach, Cumming argues, is to emphasize estimation and forget hypothesis testing.
“Meta-analysis need make no use of null hypothesis statistical testing,” he writes. “Indeed, NHST has caused some of its worst damage by distorting the results of meta-analysis.”

6. Create a Journal of Statistical Shame

OK, maybe it could have a nicer name, but a journal devoted to analyzing the statistical methods and reasoning in papers published elsewhere would help call attention to common problems. In particular, any studies that get widespread media attention could be analyzed for statistical and methodological flaws. Supposedly a journal’s editorial processes and peer review already monitor such methodological issues before publication. Supposedly.

5. Better guidelines for scientists and journal editors

Recently several scientific societies and government agencies have recognized the need to do something about the unsavory statistical situation. In May, the National Science Foundation’s advisory committee on social, behavioral and economic sciences issued a report on replicability in science. Its recommendations mostly suggested studying the issue some more. And the National Institutes of Health has issued “Principles and Guidelines for Reporting Preclinical Research.” But the NIH guidelines are general enough to permit the use of the same flawed methods. Journals should, for instance, “require that statistics be fully reported in the paper, including the statistical test used … and precision measures” such as confidence intervals. But it doesn’t help much to report the statistics fully if the statistical methods are bogus to begin with.
More to the point, a recent document from the Society for Neuroscience specifically recommends against “significance chasing” and advocates closer attention to issues in experimental design and data analysis that can sabotage scientific rigor.
One especially pertinent recommendation, emphasized in a report published June 26 in Science, is “data transparency.” That can mean many things, including sharing of experimental methods and the resulting data so other groups can reproduce experimental findings. Sharing of computer code is also essential in studies relying on high-powered computational analysis of “big data.”

4. Require preregistration of study designs

An issue related to transparency, also emphasized in the guidelines published in Science, is the need for registering experimental plans in advance. Many of science’s problems stem from shoddy statistical practices, such as choosing what result to report after you have tested a bunch of different things and found one that turned out to be statistically significant. Funders and journals should require that all experiments be preregistered, with clear statements about what is being tested and how the statistics will be applied. (In most cases, for example, it’s important to specify in advance how big your sample will be, disallowing the devious technique of continuing to enlarge the sample until you see a result you like.) Such a preregistration program has already been implemented for clinical trials. And websites to facilitate preregistration more generally already exist, such as Open Science Framework.

3. Promote better textbooks

Guidelines helping scientists avoid some of the current system’s pitfalls can help, but they fall short of radically revising the whole research enterprise. A more profound change will require better brainwashing of scientists when they are younger. Therefore, it would be a good idea to attack the problem at its source: textbooks.
Science’s misuse of statistics originates with traditional textbooks, which have taught flawed methods, such as the use of P values, for decades. One new introductory textbook is in the works from Cumming, possibly to appear next year. Many other useful texts exist, including some devoted to Bayesian methods, which Kruschke and Liddell argue are the best way to implement Cumming’s program to kill null hypotheses. But getting the best texts to succeed in a competitive marketplace will require some sort of promotional effort. Perhaps a consortium of scientific societies could convene a committee to create a new text, or at least publicize those that would do more to solve science’s problems than perpetuate them.

2. Alter the incentive structure

Science has ignored the cancer on its credibility for so long because the incentives built into the system pose a cultural barrier to change. Research grants, promotion and tenure, fame and fortune are typically achieved through publishing a lot of papers. Funding agencies, journal editors and promotion committees all like quantitative metrics to make their decision making easy (that is, requiring little thought). The current system is held hostage by those incentives.
In another article in the June 26 Science, a committee of prominent scientific scholars argues that quality should be emphasized over quantity. “We believe that incentives should be changed so that scholars are rewarded for publishing well rather than often,” the scholars wrote. In other words, science needs to make the commitment to intelligent assessment over mindless quantification.

1. Rethink media coverage of science

One of the incentives driving journals — and therefore scientists — is the desire for media attention. In recent decades journals have fashioned their operations to promote media coverage of the papers they publish — often to the detriment of enforcing rigorous scientific standards for the papers they publish. Science journalists have been happy (well, not all of us) to participate in this conspiracy. As I’ve writtenelsewhere, the flaws in current statistical practices promote publication of papers trumpeting the “first” instance of a finding, results of any sort in “hot” research fields, or findings likely to garner notice because they are “contrary to previous belief.” These are precisely the qualities that journalists look for in reporting the news. Consequently many research findings reported in the media turn out to be wrong — even though the journalists are faithfully reporting what scientists have published.
As one prominent science journalist once articulated this situation to me, “The problem with science journalism is science.” So maybe it’s time for journalists to strike back, and hold science accountable to the standards it supposedly stands for. I’ll see what I can do.
Follow me on Twitter: @tom_siegfried

sexta-feira, 12 de dezembro de 2014

The Indie Science Revolution

http://panelpicker.sxsw.com/vote/21620

Voting period for this idea type has passed

The Indie Science Revolution

An increasing number of brave researchers are venturing out from the ivory towers of academia to pursue their own independent research. This new culture of indie science attracts investigators with the freedom to develop their ideas without the confines of politics and bureaucracy often found in academic departments. Escaping the urge to "publish or perish" also affords individuals the flexibility to tackle the toughest questions in science. Further, with the declining proportion of tenure-track positions available for professionally trained scientists, many highly qualified investigators are forced to leave their beloved wet lab bench-tops. Finally, our newly founded culture of independent science combines quality research with startup culture, affording more flexibility for upcoming scientists. We will explore the ins and outs for navigating the path to becoming a successful independent scientist.

Additional Supporting Materials

Questions Answered

  1. How does one get started as an Indie Scientist?
  2. How do you fund your work as an Indie scientist?
  3. Where do Indie Scientists work?
  4. What challenges do Indie Scientists face for continuing to pursue their top interests?
  5. How do you foresee this culture expanding over the next decade?

Speakers

Organizer

Jacob Shiach Brightwork CoResearch
- See more at: http://panelpicker.sxsw.com/vote/21620#sthash.BesjLhIG.dpuf

Biotechnology: Independent streak

http://www.nature.com/naturejobs/science/articles/10.1038/nj7459-509a

Biotechnology: Independent streak

Nature
499,
509-511
(2013)
doi:10.1038/nj7459-509a
Published online
This article was originally published in the journal Nature
Scientists willing to take a risk are setting up individual research operations in rented lab space.
Ethan Perlstein was frustrated. As a non-traditional postdoc, he had spent five years running an independent lab at Princeton University in New Jersey. He wanted to continue doing what he had trained for, but a tough academic job market meant that he had no guarantees. So he decided to move to a noted biotechnology hub, California's San Francisco Bay area, to try launching his own lab without the support of an academic institution.
His goal is to validate a drug-discovery protocol and start networking with potential investors. Perlstein explored several lab spaces, and in July he signed a two-month lease for a bench at the Molecular Sciences Institute, a non-profit research facility in Berkeley, California.
OCEAN/CORBIS
Perlstein is one of a growing number of young scientists who, stymied by the lack of jobs or the slow pace of research in academia, are pursuing cutting-edge research in their own spaces. Research tools and lab areas are becoming more affordable, particularly in the communal set-ups dubbed biohacker spaces, which seek to enable biological experimentation for hobbyists as well as for entrepreneurs. Funding schemes aimed at early-stage companies are also starting to offer a way to pursue an independent science career. Despite the risks, the option of launching an individual research operation is gaining traction throughout the United States and Europe.
Such routes, however, involve striking out into the unknown. Some non-profit, volunteer-driven hacker spaces are struggling to stay afloat, and it is not yet clear how independent research operations will become sustainable, especially if their work has no immediate practical applications. Young scientists eager for this brash brand of independence should consider their research needs, find out which spaces are optimally set up to help them, and determine how best to secure financial support.

Hacker craze

The first biohacker spaces were fuelled by the do-it-yourself biology movement, in which untrained hobbyists started running biotechnology experiments in their kitchens and garages (see Nature 467, 650–652; 2010).
These days, both amateurs and professionals are seeking out cheap lab space. The set-ups vary: hackers can rent a stretch of lab bench at GenSpace in New York, for example, for US$100 per month including access to reagents and some biotechnology instruction. But scientists working on specific projects often have more specialized needs, and a new model is emerging in the United States. The hybrid 'hackubator' fuses the independence and affordability of hacker spaces with the entrepreneurial bent of biotech business incubators.
Bio, Tech and Beyond, a hackubator space that opened this month in Carlsbad, California, charges $400 per month for a lab bench — much less than the roughly $900 per month of conventional biotech incubators. Members get access to centrifuges, cell-culture incubators, plate robotics and three-dimensional printing, as well as help with writing grant applications.
“Biotech incubators offer company spaces, hackubators offer pre-company spaces — when it's just you and an idea, but you need the equipment and connections to biotech and pharma to get an idea off the ground,” says Ryan Bethencourt, an entrepreneur involved in planning two biohacker spaces in the San Francisco area.
Ethan Perlstein: “I don't want to give up doing science and I'm willing to go the distance to find a way to make it work.”
Several cities are encouraging the development of hacker spaces to create jobs and generate tax revenue. Joseph Jackson, co-founder of Bio, Tech and Beyond, got his organization's space essentially rent-free from the city of Carlsbad; in exchange, he is supposed to help launch eight companies within two years. He already has eight pilot users and 12 further requests for space. “If we can't make this model work here, it won't work anywhere,” he says.
Brightwork CoResearch, a biosafety-level-2 facility for independent scientists, is set to open in August next to Rice University in Houston, Texas, home to one of the country's largest medical centres and a fledgling biotech community. Brightwork's initial funding comes from a stem-cell biologist and a local entrepreneur. There will be 20 benches dedicated to full-time researchers and another 20 for part-time researchers; almost one-quarter of the spaces have already been assigned. Most of the researchers hope to form companies, but sustaining their work won't be easy. “The big question is, how will groups fund their research,” says co-founder Jacob Shiach. “The only thing that matters to me is that people are able to push the science they love forward.”
Europe's budding biohacker scene includes La Paillasse in Paris: the continent's largest biohacker space, with more than 30 members, who pay what they can for the space (even as little as €2, or US$2.60) and use mostly donated equipment. Co-founder and president Thomas Landrain, a PhD student at the Institute of Systems and Synthetic Biology in Evry, France, says there are ten projects currently in development; at least three, including one focused on producing cheap ink from microbes, could become start-up projects. La Paillasse is growing rapidly and, with public funding and support from the mayor of Paris, will soon move to a larger building in the city centre, says Landrain.

Independently wealthy

Once they have found a space for their work, scientists still need to find funding streams. That may mean taking on contract research, using crowd-funding to get enterprises off the ground or winning speciality grants, such as the small business innovation research grants from the US National Institutes of Health and the US National Science Foundation.
Saul Griffith is the co-founder of OtherLab, an independent research lab in San Francisco. His company gets roughly 40% of its revenue from grants to conduct early-stage, high-risk applied research on projects ranging from solar energy to robotics for agencies such as the US Department of Energy and the Defense Advanced Research Projects Agency. Another 20% is from contract research for companies such as Ford and General Electric. The rest comes from developing intellectual property and selling products — notably the OtherMill, a small, computer-controlled mill that can cut everything from circuit boards to jewellery.
ANDREA DUNLAP
Saul Griffith funds his independent research in areas such as robotics using grants and contract work.
UBiome — launched from the California Institute for Quantitative Biosciences, a start-up incubator at the University of California, San Francisco — gets its funding in small chunks by selling microbiome-profiling kits. For $89, it will sequence the genomes of the microbes living in a person's mouth, gut, nose or genitals. It gives individuals insight into their bacteria, but co-founder Zachary Apte also wants to mine the data to uncover insights such as how eating habits influence microbiomes. “I was ready to do my own research and had my own ideas to explore, but it takes a long time to get there taking the academic path,” he says. His is not the only outfit funded by the public: earlier this year, three biohackers launched a crowd-funding campaign to raise the money to bioengineer a glowing plant (see Nature 498, 15–16; 2013). They made just under $500,000.
A few funding schemes specifically provide early-stage support to high-risk, high-reward independent ventures. Shiach has just launched SynBio axlr8r, a programme to jump-start synthetic-biology companies with funding from SOS Ventures, a venture-capital firm in Kinsale, Ireland. “The goal of SynBio axlr8r is to take an idea through proof of concept to form a company within 90 days,” he says. The first batch of 10–20 successful applicants will get US$30,000 each and a space at a science incubator in Cork, Ireland.
Through a scheme called Breakout Labs, the Thiel Foundation in San Francisco funds early-stage companies working on radical, big-risk ideas that are unattractive to federal funding and venture capital. Grants of $350,000 help recipients to reach technical milestones, at which point they can start to attract more conventional grants or investments. “I started a commercial enterprise because I wanted tools that didn't exist, to conduct my research,” says Todd Huffman, who used a Breakout Labs grant to support 3Scan, an early-stage company that he co-founded to develop a knife-edge scanning microscope that simultaneously cuts and scans tissue slices to create three-dimensional models of samples. “I wanted to build these tools during my PhD and my adviser didn't think it was a good use of time,” he says. Huffman dropped out of his PhD programme but maintains an interest in neuron morphology; after establishing 3Scan, he hopes eventually to return to his PhD with a new set of tools in hand.
Darren Zhu received a $100,000 two-year grant from the Thiel Foundation to leave university and become an entrepreneur. He is exploring ways to engineer organisms to produce novel molecules, a project that could help him to find a niche as the pharmaceutical industry continues to outsource early-stage research and development. “At this stage of my life, I can afford to take risks, to swing for the fences and see where it takes me,” he says. In addition to his Thiel grant, he has money from the Bill & Melinda Gates Foundation in Seattle, Washington. He used it to buy lab equipment from liquidated firms, with which he has furnished an independent, industrial lab space in Mountain View, California.

Overcoming the odds

Zhu says that one of the bigger hurdles of pursuing an independent path is that much of the biotechnology field still places a premium on “old-fashioned credentialling” — publishing work in prestigious journals or having done a postdoc at a reputable institution. It is a challenge, he says, but one he has overcome by securing high-profile grants and fellowships.
The first challenge that Perlstein encountered was finding a space that met his needs. He was intrigued by the mix of hobbyists and professionals in biohacker spaces but, in the end, they just did not work for his specialized research. The space he eventually settled on is comparatively pricy at roughly $2,000 per month — but it offers a fully stocked yeast lab that will allow him to hit the ground running, conducting the six weeks of experiments that he anticipates needing to develop a rapid yeast screen for rare-disease therapeutics.
Bethencourt is helping to plan the Counter Culture Labs hacker space in Oakland, California, which will provide lab space to at least 50 paying members from this autumn onwards. But, seeing the need for more specialized spaces, he has also co-founded a small therapeutics-focused hacking space, called Berkeley Biolabs, which is set to open this summer.
Perlstein notes further challenges such as finding insurance to cover mishaps at a rented lab bench. His biggest hurdle, however, may be determining whether his research will translate into a viable company — and whether he wants it to.
With funding and positions growing more difficult to find in academia, many more scientists may become willing to take on the risks. And biohackers looking to continue their work in the face of a dismal funding scene will ultimately form their own experimental units. “People are taking control,” says Perlstein. “I don't want to give up doing science and I'm willing to go the distance to find a way to make it work.”

Author information

Affiliations

  1. Virginia Gewin is a freelance writer based in Portland, Oregon.