One of the challenges of managing "incredibly focused, driven and intelligent people", such as research scientists, is the need to support their research while impressing on them the importance of complying with a plethora of regulations that govern their work. A delay may let another institute or group seize the initiative and claim the scientific breakthrough. There are no prizes for publishing your research second.
For Neil Hawthorne, head of safety, health and environment at the Laboratory of Molecular Biology (LMB), and his team of safety and health professionals, it is a delicate balancing act.
He has to enforce the rules governing some very hazardous materials, from disease-causing bacteria to chemicals and radiological sources that are essential to the LMB's work examining and testing the building blocks of life.
"Science is god here," says Hawthorne. "Sometimes scientists can be so focused that any distraction is unwelcome. The key to gaining their cooperation is to concentrate on enabling their work rather than holding it up."
Founded by the Medical Research Council (MRC) more than 50 years ago, the LMB carries out cutting-edge research on biological processes at the molecular level. It counts ten Nobel prize-winners among its alumni and now attracts leading researchers from more than 50 countries.
The main Cambridge site, a chromosome-shaped eight-storey architectural showpiece that opened in 2013, has two laboratory blocks connected by a central atrium and is located at the heart of an expanding biomedical campus in the suburbs to the south of the city. There is also a nuclear magnetic resonance facility, MRC offices and a biomedical services facility in the city, which Hawthorne also oversees as part of his portfolio. More than 600 scientists and support staff work at the LMB's Cambridge sites.
The LMB building comprises three levels of laboratory space, separated by an equal number of engineering floors. The facility also houses several small electronics and mechanical workshops.
The Laboratory of Molecular Biology (LBM) is regulated for the work it carries out on chemicals, pathogens, toxins (biological), plants and using ionising and non-ionising radioactive materials. The regulatory body is defined by whether it relates to human health, environmental protection or other uses.
Schedule 5 toxins and organisms and high activity sealed sources for radiation ionising materials that fall under the Anti-Terrorism Crime and Security Act 2001 are the most heavily regulated and are overseen by the Home Office. The introduction of the legislation has had a big impact on the LMB's work, tightening procedures for procurement, storage and use of radiological and biological agents. Hawthorne will often deal with counter terrorism and security advisers to ensure that the facility meets stringent security requirements.
The complexities surrounding biosafety mean that, "with the pathogens we handle, you have to make sure that you are meeting multiple pieces of legislation just for one pathogen".
The Health and Safety Executive (HSE) is responsible for notifications for genetically modified materials that fall under the Genetically Modified Organisms (Contained Use) Regulations 2014, which operates similarly to a licensing process. It also covers wild type (the non-mutated version of common genes and organisms) under the Control of Substances Hazardous to Health Regulations 2002 (COSHH).
The HSE also enforces chemicals under COSHH, the Dangerous Substances and Explosive Atmospheres Regulations 2002 and the Explosives Regulations 2014. The Chemical Weapons Convention (CWC) UK National Authority, part of the Department for Business, Energy and Industrial Strategy, regulates chemical weapons and CWC precursors while the Home Office is responsible for enforcing controlled drugs and drug precursors.
Animal pathogen-related research work is covered by the Specified Animal Pathogens Order, which falls under the Animal Health Act 1981. The Department for the Environment, Food and Rural Affairs (Defra) used to enforce this area but is now undertaken by the HSE.
The health and safety regulator also takes responsibility for enforcing the radiation non-ionising work, which is part covered by the Control of Electromagnetic Fields at Work Regulations 2016. The radiation ionising research falls between the HSE (human health) and the Environment Agency (environmental protection).
While the HSE has yet to carry out a general inspection of the LMB facilities, Hawthorne says that "its specialist [biosafety] units do carry out periodic visits".
Defra and Fera, the enforcement body for plant health, and occasionally the Forestry Commission, oversee the research work involving plants. Hawthorne explains that most of his interactions with Defra and Fera involve the agencies checking permits for restricted organisms and materials.
Four giant towers handle the building's air supply, filtering fresh air through the labs via interstitial floors. Carbon dioxide and liquid nitrogen for freezing samples are pumped from onsite bulk tanks through an extensive tunnel network in the basement and up to fill stations on the laboratory floors.
The lab hazards -- biological, chemical and radiological -- account for 75% of Hawthorne's operational safety responsibilities and are tightly managed. Risk assessments drive everything. Those for genetic manipulation, one of the most tightly regulated areas of work at the LMB, follow a host-insert-vector process to identify the controls. The host, say a bacterium, into which genetic material is inserted must be assessed -- from high risk in the case of the Ebola virus to low for a benign soil-borne organism. The assessment also considers what material is being put in the host and the carrier (or vector) for insertion.
The controls fall into four containment levels (CLs). The lowest, CL1, covers organisms that cause no disease in humans. The highest, CL4, is for severe human disease agents with no treatment available, such as Ebola and emerging, virulent diseases, including Nipah and Hendra which can cause acute respiratory syndrome and fatal encephalitis (brain inflammation).
LMB does not undertake any CL4 research; most is CL1. However, genetic modification and wild type research (on the non-mutated versions of common genes and organisms) is covered by both CL1 and CL2. Control measures vary for all classes. To work with staph aureus, a bacterium associated with skin infections, researchers don nitrile gloves, for example. For non-pandemic influenzas, which pose a respiratory risk, working in a sealed safety cabinet is required. At CL2, the main challenge, says Hawthorne, is making sure there is a consistent approach: "CL3 is high risk, while CL1 is low to negligible risk. The issue with CL2 is that it fits somewhere in the middle and relies much less on engineering controls and often more on practices."
Later this year, the LMB will open its first CL3 facility in the new building to work on tuberculosis (TB). CL3 organisms can cause severe human diseases and, though treatment is available, containment is critical to protect the scientists. The new lab is sealed securely with hefty bolted window frames reminiscent of those on ships. Service pipes enter the room through special sealed connectors and high-efficiency particulate air extractors filter the air. Scientists will handle the TB bacteria in sealed glove cabinets.
In early 2016, Hawthorne kicked off a series of "engagement visits", dropping in on the researchers at their workstations to help his team better understand the science that is undertaken at the LMB and to get the scientists more used to an OSH presence.
"Historically, inspection and audit wasn't done here at the LMB, so that's been a fundamental change for them," Hawthorne says. "Traditionally, safety was less of a priority. There are legacy issues that we are still working on in order to further improve standards and drive safety and safety culture forward."
Ergonomic and manual handling hazards are focal points, especially as scientists can spend long stretches at workstations. His team ran an awareness campaign to highlight repetitive strain injuries and musculoskeletal problems and to remind staff to report any issues, triggering a "fairly big spike" in notified cases.
Hawthorne and his team then set up an ergonomic improvement team, which includes managers/staff in key priority areas, and used the Health and Safety Executive's assessment of repetitive tasks tool to identify areas for improvement and changes that could be made to tasks to reduce ergonomic issues.
An example of the improvements is in the LMB's room where thousands of small zebrafish are bred for TB research. To prevent the researchers from having to remove and replace the shoebox-sized plastic tanks, Hawthorne has asked for the racks to be configured at waist-height.
The diverse range of biological, chemical and radiological hazards means that the LBM deals with a variety of regulators.
On very rare occasions a research scientist may question why such stringent controls are required.
"[I have had one scientist say], 'Well, I don't agree with that. Can you go back to the government and tell them that they are wrong and ask them to change the legislation? They don't understand how it's blocking science'."
Historically, inspection and audit wasn't done here at the LMB, so that's been a fundamental change for them
Hawthorne adds that it is important that his team supports the scientists, using their own scientific background to interpret the legislation and apply it so that it enables the research to proceed.
Fortunately, Hawthorne has a degree in microbiology, coupled with years of lab-based research for a National Health Service (NHS) trust and the Health Protection Agency, most notably in the latter's containment facilities at Porton Down where he handled anthrax.
"I was an experienced CL3 worker [when I moved to the HPA in 2007] because I'd done a lot of TB work at Sandwell and West Birmingham NHS Trust."
In 2009, he moved into a full-time safety role and, while working at Warwick University as its health and safety (biosafety) adviser from 2011 to 2014, he secured a NEBOSH diploma before later moving to the MRC. He heads a team of four safety advisers. All of them have the scientific background that Hawthorne insists is critical to the role.
"With a lot of the biological safety, it's incredibly technical and complex. You can be talking about genetically manipulated organisms and molecular genetics," he says. "Unless you've done it, I don't think you could support the scientists."
In such an innovative environment, keeping up with new technology is critical not least so that the science can "stay ahead of the curve". LMB's researchers are breaking new ground using CRISPR/Cas9, a genome editing tool that allows the research scientists to remove, add or alter sections of the DNA sequence at a much greater speed.
Much of the team's time is taken up "coaxing, coaching and mentoring" the scientists. They are there to be critical friends -- "to get the researchers to pause and reflect [and come up with their own solutions]".
In such a pressured environment, his team has to carefully balance safety controls with academic freedom. The scientists write the risk assessments for their experiments, which is rarely a problem for the younger researchers, though their older ones sometimes need more support as they have not been brought up with safety and health.
"It's about building that trust and trying to get them to understand that what we are asking them to do is a legal requirement, that it is in their best interests and is not particularly onerous," Hawthorne says.
"We are always on hand to help. They often have all of the answers, so it is about asking the right questions. One way to do that is to have more specific risk assessments that ask those questions. A blank page is daunting for everyone."
But embedding a safety culture is still work in progress in low-risk areas. Persuading scientists to wear their lab coats remains a challenge, he concedes: "We have academics and researchers who start and wear lab coats and due to peer pressure they stop wearing them."
Scientists can procure their own materials for research, which presents its own challenges. Any carcinogenic, tetragenic or potentially explosive material must be reported to his team. But lesser materials, even down to agar plates -- petri dishes with a seaweed derived medium that encourages cells to form colonies -- can present a risk.
"We've been heavily involved with them because you are talking about powders, which can be a potential allergen," he says. "In a powdered form, there is quite a hazard there, so we now use powder stations as a primary engineering control."
It's incredibly technical and complex. You can be talking about genetically manipulated organisms ... Unless you have done it [yourself], I don't think you could support the scientists
Potentially hazardous materials can also move freely around the building. Hawthorne remembers one incident involving shigella, a leading bacterial cause of diarrhoea and a Schedule 5 restricted organism. A scientist had approached a colleague for a sample but the SHE team stepped in and asked them not to share it because the facility did not meet the strict security requirements.
Another potential issue is the custom-made pieces of kit that scientists can procure from the on-site workshops. The majority are built to the highest standards but, on one occasion, a risk assessment had not been carried out on a bespoke machine and one of the bottles shattered, resulting in a near-miss. The scientist reported it to Hawthorne's team.
Additional controls, including pressure-rated bottles, were agreed but the scientist still believed that the risk was their own to accept.
"Being naturally intelligent people and considering the pressure they put themselves under to achieve, their perception of risk, or personal acceptance of risk, can differ from that of a health and safety professional. Sometimes, it is a matter of support and education, which is a fine balance," he says.
The LMB's new building design offers some OSH advantages. The decision to incorporate floor-level sluices means that domestic services staff do not have to lift heavy containers into sinks to dispose of liquids. It is not perfect, however.
"When they installed the liquid nitrogen bulk tank, they didn't consider the tunnels that [the piping] runs through," says Hawthorne. "What happens if there is an accident, which could be a foreseeable release? After moving into the building other areas were prioritised, so I reviewed the current risks and ensured that additional controls were installed."
This comprised the installation of oxygen depletion and CO2 enrichment monitoring in the tunnels, which could have been designated as a confined space.
As well as the materials entering the building, his team also has to monitor the waste generated. Biological waste, which goes into standard yellow bins for specialist off-site disposal, poses no problem. Radiological waste is properly logged and is also easily managed. The focus of most improvement has been with the chemical waste.
"Six months ago, I dealt with an issue that related to a possible risk associated with a chemical called piranha solutions [a cleaning agent containing hydrogen peroxide and sulphuric acid], which can release gas and over-pressure the bottles, posing a risk to our hazardous waste team," he recalls.
"We are now buying in standard containers, which we supply through our stores department with standard labels so the scientists can tick what hazard it is, based on CLP classifications, write on it what it contains and where it was generated."
Last November, the LMB staged a mock chemical spill emergency response exercise with Cambridge Fire and Rescue Services. The exercise was insightful. "We've got an approximate inventory of what we've got in the building and waste stores but down to what is in the building at any one time [because so much is stored], we don't," he admits.
"We did question if we needed to get down to that level for the chemical wastes we store but the fire service was happy with the way we managed it and it might have been disproportionate."
Far more important is how the LMB would respond to a major fire on site.
The LMB is a global leader in electron microscopy, which allows inspection of structures at the atomic level. It is one of only a handful of UK research institutes to house two top-of-the-range, multi-million pound Titan Krios electron microscopes and has plans to install a third.
While Cambridge Fire & Rescue Services is not responsible for protecting material goods in the event of fire, some equipment, including the EMs, is critical to the LMB's business continuity.
"We have agreed that if they can, they will try and stop [fire] spreading," he says, adding that they can switch off the air handling and electricity to assist containment.
The radiation rooms and the containment suites are "let it burn" areas, as are some of the laboratories. Consequently, Hawthorne occasionally has to reiterate the importance of ensuring that tests using equipment that can trigger fires are carefully carried out.
"It is important to communicate to our scientists that any fire, even a small one, could have a potentially large impact on research/business continuity. Therefore, we need them to think about how they work as it will not be as simple as walking straight back into the building."