As the year comes to a close, it’s only natural to speculate about what lies ahead. In the laboratory world, the “lab of the future” is always a hot topic. Augmented reality, robots as lab personnel, the complete elimination of paper—these subjects are all common discussion points around this time of year. But the fact is, we’re still years away from that version of a laboratory. Once the clock strikes 12:00 a.m. on Jan. 1, 2016, labs around the world will remain mostly unchanged. Spectrometers and chromatographs will still take up bench space, freezers and refrigerators will still be noisy and the lighting will still not be quite right.
But that’s not to say the lab of 2016 is without its opportunities—and challenges.
The discussion around the revolutionary CRISPR-Cas9 genome editing technique is expected to continue as scientists work to improve the system daily. Refined approaches and breakthroughs occurred frequently in 2015, even as scientists called for a moratorium on the controversial system.
While there will always be scientific challenges in a laboratory, participants in a recent panel titled “Eye on the Future” at the R&D 100 Awards & Technology Conference pointed to two less traditional challenges the science and technology industry must overcome.
Daryl Belock, VP of Innovation and R&D Collaboration at Thermo Fisher Scientific, said one of the biggest challenges in coming up with the next generation of technology is finding the right talent to do so.
While Thomas Mason, Director of Oak Ridge National Laboratory (ORNL), and Dean Kamen, entrepreneur and inventor, agreed with Belock, they also pointed to another hardship facing the science industry—poor public perception.
Challenge 1: Scientific workforce
According to the National Science Board’s (NSB) biennial Science and Engineering Indicators 2014 report, the science and engineering (S&E) workforce has grown steadily over time. Between 1960 and 2011, the number of workers in S&E occupations grew at an average annual rate of 3.3 percent, greater than the 1.5 percent growth rate of the total workforce. Additionally, during the 2007-2009 recession, S&E employment compared favorably to overall employment trends.
While the idea of a shortage in the field has been pervasive recently, the numbers seem to indicate otherwise. It’s not so much finding employees, it’s finding the right employee with the right skill set.
“There always seems to be a small group of very talented people that stimulate breakthroughs in innovation,” said Belock. “It’s very easy to fall into a short-term vision of the future, where teams get into incrementalism in terms of what they are bringing to the market. Taking a longer-term view and developing talent, and rare talent, is critical.”
Terry Adams, Shimadzu Scientific’s Vice President of Marketing, agrees that a long-term vision, and cultivating a culture that is committed to the long-term, is half the hiring battle these days.
“We’re at a stage where we need experienced people, but they come with history and baggage based on their past jobs or what they perceive this job to be,” Adams told Laboratory Equipment. “[New employees] are surprised about our patience, how deliberate we are, how much planning we do—we work off of a very deliberate 9-year plan in 3-year increments. We’re not driven quarter to quarter or half to half. We’re thinking year to year.”
Like every other industry, the aging of the baby boomer generation will have/is having significant implications in science and technology. Five years ago, the oldest baby boomers were 60, and still a productive part of the workforce. In fact, according to the NSB report, between 1993 and 2010, increasing percentages of scientists and engineers in their 60s reported they were still in the labor force. Whereas 54 percent of scientists and engineers between the ages of 60 and 69 were employed in 1993, the comparable percentage rose to 63 percent in 2010.
However, more recent estimates from the Bureau of Labor Statistics indicate that the oldest baby boomers—of which about 10,000 turn 65 years old every day—have begun the wave of retirements, significantly shifting the country’s age demographics
“Fifty percent of our staff has been with us less than 10 years,” said ORNL’s Mason. “It’s tremendous [and] exciting, lots of new people and ideas coming in. But how can we create in them the kind of culture that will allow us to continue to push the envelope? That’s probably the thing I feel the greatest need around.”
In industry specifically, a popular approach to hiring young staff members is to train them as early as possible, even while they are still in school. For example, Shimadzu (and other equipment manufacturers) have established Centers of Excellence in research-heavy universities. These centers are typically gifted with millions of dollars of a manufacturer’s state-of-the-art equipment. Students working in the center are then heavily exposed to the company’s equipment and techniques well before they look to enter the workforce.
“[Because] the students are already being trained on our instruments, we can pluck them right out of school to start the lower-tier jobs and move everyone else up through the ranks,” Shimadzu’s Adams explained. “We try to grow our own talent. [The students] come in already knowing our technology and science, now it’s time for them to understand the business world. If we can move them up through the corporate ladder, they do fit the culture. They are already a part of it.”
Adams also commented that, recently, the pool of qualified candidates has featured more women and minorities than in the past. According to the 2014 NSB report, women remain underrepresented in the S&E workforce, but to a lesser degree than in the past. Additionally, the number and percentage of undergraduate and master’s degrees in most major S&E fields has increased for both woman and minorities since 2000.
“The only thing that has yet to be commoditized, the only thing that will add value is innovation,” said Kamen, the inventor of the insulin pump and Segway. “To do that innovation, more than ever, will require people. Smart people with vision and courage that will focus on the right things.”
Challenge 2: Public perception
The general public and scientists express strikingly different views on science-related issues, according to a Pew Research Center report that was published January 2015. The report found significant differences in views on 13 science-related issues, the largest of which include:
• A 51-percentage point gap between scientists and the public about the safety of eating genetically modified foods– 88% of American Association for the Advancement of Science (AAAS) scientists think eating GM food is safe, while 37% of the public believes that.
• 42-percentage point gap over the issue of using animals in research– 89% of scientists favor it, while 47% of the public backs the idea.
• 40-percentage point gap on the question of whether it is safe to eat foods grown with pesticides– 68% of scientists say that it is, compared with 28% of citizens.
• 37-percentage point gap over whether climate change is mostly caused by human activity– 87% of AAAS scientists say it is, while 50% of the public does.
“Scientists get an A+ for the accelerated rate at which technology is happening, but we get a C- for engaging the global public in understanding why it’s so important, why we need to keep moving with it and how we can do it in a responsible way,” said Kamen. “If we don’t deliver that clear message over and over again until the world accepts it, we’re headed for a train wreck.”
Overall, the report—based on two surveys performed in collaboration with AAAS—suggests science holds an esteemed place among citizens and professionals, but both groups are less upbeat about the scientific enterprise than they were in 2009—a concerning fact, and something to monitor closely in the coming years.
From the public perspective, the trust decline could be due to a series of high-profile scientific papers found to be fraudulent, the most popular of which was a study claiming “acid baths” offered an easy pathway to the generation of new stem cells called STAP. The papers, along with the authors from RIKEN, immediately gained notoriety. However, no one could duplicate the results, and complaints started forming just a few days after the papers’ release in January 2014. Six months later, Nature retracted the papers, citing critical errors and falsified data. But the damage was already done. News of this “amazing” new stem cell had already hit mainstream media, and the scandal—which saw one co-author take his own life—became a story all to its own.
“One of the concerns I have is you have instances where people have actually been doing deceitful things, and that gets discovered—in a sense you can say that is the system working or self-correcting. However, then you juxtapose that against some of the areas of science that are politically or social controversial, like climate change, for example. In the minds of the general public, it’s hard to extinguish fraudulent behavior. If you’re not an expert in the field, it is extremely difficult to distinguish those cases,” said Mason.
Despite that, the Pew Research Center found there is still broad public support for government investment in scientific research. Seven in 10 adults say government investments in engineering and technology and basic scientific research usually pay off in the long run. Some 61 percent say government investment is essential for scientific progress, while 34 percent believe private investment is enough to ensure that scientific progress is made.
CRISPR-Cas9 is a genetic engineering technique invented by molecular biologist Jennifer Doudna that is capable of quickly, easily and inexpensively performing precise changes in DNA. Cas9, a naturally occurring protein in the immune system of certain bacteria, acts like a pair of molecular scissors to precisely cut or edit specific sections of DNA.
Invented in 2012, interest in the technique has increased dramatically in the past two years, prompting scientists to gather at a summit earlier this month to establish guidelines for its responsible use in the future.
The main concern with CRISPR (and similar techniques) is that it can be used to perform germline genetic modifications, which means making changes in a human egg, sperm or embryo. These modifications would be passed down for generations, impacting an entire lineage rather than just one person. However, at the same time, CRISPR’s ability to edit human DNA could eliminate genetic diseases.
Fortunately, the recent uptick of interest in the technology has been accompanied by dramatic improvements in the past year—including multiple enhancements in just the last few months.
While Cas9 is highly efficient at cutting its target site, a major drawback of the system has been that, once inside a cell, it can bind to and cut additional sites that are not targeted. This has the potential to produce undesired edits that can alter gene expression or knock a gene out entirely, which could lead to the development of cancer or other problems.
But, researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have devised a way to dramatically reduce “off-target editing” to undetectable levels.
Using previous knowledge about the structure of the Cas9 enyzme, Feng Zhang and colleagues were able to predict that replacing some of the positively charged amino acids in DNA with neutral ones would decrease the binding of “off-target” sequences much more than “on-target” sequences. After experimenting with various changes, Zhang’s team found that mutations in just three of approximately 1,400 amino acids dramatically reduced “off-target” cuts.
The newly engineered enzyme, which the team calls enhanced S. pyogenes Cas9, or eSpCas9, will be useful for genome editing applications that require a high level of specificity. The lab has made the eSpCas9 enzyme available for researchers worldwide.
“We hope the development of eSpCas9 will help address some of [safety] concerns [related to off-target effects], said Zhang, who was a speaker at the International Summit on Human Gene Editing. “But we certainly don’t see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use.”
Additional research out of Harvard’s Wyss Institute has recently added another layer of safety to CRISPR with the ability to reverse the spread of imposed genetic traits.
George Church and Kevin Esvelt developed molecular confinement mechanisms to prevent gene drives from functioning in the wild by manipulating CRISPR’s biological components. By separating the guide RNA and the Cas9 protein so they are not encoded together in the same organism, or by inserting an artificial sequence into the target gene, gene drives can only be activated in lab organisms.
According to Harvard, using this safeguard, essentially any population-level change mediated by a gene drive could be overwritten if the need ever arose. In such a case, the originally imposed trait would be reversed and the biological machinery of the CRISPR gene drive system—the guide RNAs and the Cas9 protein—would remain present, albeit inactive, in the DNA of organisms.
What’s more, the reversibility mechanism isn’t just a useful backup in case a gene drive ever had an unexpected side effect—the researchers believe the ability to impose or reverse gene drive effects could one day prove powerful for the management of disease-transmitting organisms, invasive species and crop-destroying insects.
“The gene drive research community has been actively discussing what should be done to safeguard shared ecosystems, and now we have demonstrated that the proposed safeguards work extremely well and should therefore be used by every gene drive researcher in every relevant lab organism,” said Esvelt.
Opportunity: CRISPR guidelines
The International Summit on Human Gene Editing—hosted by the U.S. National Academies, UK Royal Society and the Chinese Academy of Sciences—concluded on Dec. 3 after three days of discussion on the scientific, ethical and governance issues associated with human gene editing technologies like CRISPR.
The 12-member organizing committee acknowledged that basic and preclinical research is very much needed and should proceed; however, modified cells should not be used to establish a pregnancy.
In fact, the committee cautioned against the clinical use of gene editing in regards to the germline, which can pass edits and mutations on to subsequent generations.
“It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application,” the committee wrote in its statement.
However, the green light was given to clinical applications of gene editing that are directed toward altering somatic cells only—or those cells whose genomes will not be transmitted to the next generation. Since the proposed clinical uses are intended to affect only the individual who receives care, the committee approved use of the technology within “existing and evolving regulatory framework.”
Overall, the committee stopped short of calling for a permanent ban on editing human embryos and germline cells.
“As scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis,” committee members wrote.
That regular basis will begin immediately, with the national academies that co-hosted the summit pledging to take the lead in creating an ongoing international forum. Over the next year, scientists and ethicists from the U.S., UK and China will convene to examine some of the issues raised at the meeting, and release an additional report with more concrete guidelines in late 2016.