BASECLEAR 25 YEARS OF DNA EXPERTISE
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W Welcome to BaseClear
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Exactly 25 years ago, we came up with the idea to start a company providing essential services in the analysis of genomics. It was the time that the first automated DNA sequencing machines came on the market, and scientist were thinking about the first genome projects: bacillus, yeast and of course the Human Genome Project. The analysis was time-consuming: we could process about ten samples a day on a single machine. Technological advances now allow for simple, high throughput analysis of the most complex genetic materials. All those years, BaseClear has been able to stay ahead of the field through a focus on innovation and development. We are now the largest fully independent genome specialist in Europe.
facilities at Leiden Bio Science Park this year, where a state of the art and sustainable laboratory building was created to make us thoroughly future-proof. One of our aspirations was to have a special lecture room for meetings: a perfect place for clients, collaborating partners, students and BaseClear’s employees to exchange knowledge and ideas. We are very happy to be able to contribute to the field in this way.
Apart from our twenty-fifth anniversary, we have another reason to celebrate. We moved to our new
Bas Reichert, CEO and founder Erna Barèl, COO and founder
With this magazine, we hope to give you an impression of what BaseClear built over the last twenty-five years, where we are right now, and to share with you our ideas for the future. We wish you pleasant reading,
COLOPHON PUBLISHER Barry Reede
ORDERING PARTY BaseClear
SALES & TRAFFIC Marloes Oink
COORDINATION BASECLEAR Patrick Koning
EDITING Moniek Veltman
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PHOTOGRAPHY Jean-Pierre Jans
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ART DIRECTION Colette Korteweg NEW BUSINESS Marja Maars Wesley Dekker
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DNA
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DNA is Everywhere BaseClear works with DNA, which is found everywhere on this planet. Therefore, DNA analysis has many different applications, from food to washing powders.
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Current DNA technology allows for simple, high throughput analysis of the most complex genetic materials. This offers a lot of opportunities for a DNA expert like BaseClear. As CEO Reichert explains: “DNA is found everywhere on this planet. It is part of humans, animals, plants and microorganisms. Bacteria, fungi and viruses populate lakes and oceans, as well as the air and soil. The wide range of organisms and habitats makes that DNA analysis has many different applications and, consequently, a profound impact on our society.”
Expertise in Microbial Genomics DNA research is often associated with human DNA analysis, for example forensic DNA testing, paternity testing or genetic diagnostics. Although BaseClear is involved in human DNA research, this is not its main focus. The company has built up a strong expertise in DNA analysis of microorganisms.
DNA analysis has many different applications and, consequently, a profound impact on our society.
For example, BaseClear worked with a partner organisation to modify the DNA of a bacterial enzyme that is used in washing powders. This optimised enzyme allows clothes to be washed at lower temperatures, which is a win-win for both consumer and environment. Microbial Profile Another example of how analysis of genetic material can help consumers is a service provided by BaseClear’s subsidiary company MyMicroZoo. This company sells a kit for the microbial analysis of the gut flora, with which anyone who is interested can send a sample to the lab. Analysis of the genetic material in this sample generates a personal microbial profile, showing the number and diversity of bacteria in the gut flora. A low diversity, for example, can be an indicator that the person does not have a varied diet. Results are presented in an online portal where participants can compare their results to those of other groups such as vegetarians or athletes. Based on the profile, participants receive nutritional advice. Together with dieticians, BaseClear is now extending the service to include comprehensive nutritional and lifestyle advice. Plant Complexity A growing market for BaseClear is the analysis of plant DNA. Strikingly, the genetic material of some plants is much bigger and more complex than human DNA. Future Genomics Technologies, a collaboration between BaseClear and Leiden University, has recently sequenced the complete DNA of an orange tulip. This tulip has 35 billon base pairs of DNA, which is easily ten times as much as are found in human DNA. A new DNA sequencing apparatus developed by British Oxford Nanopore Technologies performed this mammoth task. Understanding the DNA of this tulip allows faster and more sustainable crossbreeding. This can help to produce plants with desirable characteristics, such as a resistance to diseases, and reduces the need for pesticides.
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B BaseClear: 25 years of innovation and growth The founders of BaseClear, Bas Reichert and Erna Barèl, started the company as alumni of Leiden University. They experienced all the phases from a two-person starter to the biggest independent genome specialist in Europe.
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Reichert and Barèl conceived the idea for BaseClear in 1993, while they were studying biology at Leiden University. Reichert: “While most of our co-students started a PhD or left biology, we wanted to stay in the field, not as scientists but as entrepreneurs. We both worked with sequencing technologies during internships and found expertise in these techniques was lacking amongst many users. This experience inspired us to start a service-oriented business for the analysis of DNA. After some market research, we came to the conclusion that there was no shortage of potential clients.”
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Early Days In the early days of BaseClear, Reichert and Barèl did everything themselves. In a small lab in Rijnsburg, they sequenced DNA samples with a leased sequencer, driving around in an old Citroën Visa to customers to deliver the results. In 1994, only five months after its founding, the company moved to a lab in a shared premises in Leiden. This allowed the company to be close to the university and to several partners and clients. In the same period, BaseClear got its first large assignment: Reichert and Barèl were asked to sequence a full gene cluster of DNA for a pharmaceutical company, a
We always made sure we had the latest technology in-house. large project in those days. Another boost came when BaseClear participated in a large European sequencing project of Arabidopsis in 1995. Bigger Housing Meanwhile, the workload had grown so much that more staff was needed, so more people were hired and the company grew. Reichert continued to perform lab work until around 1998, while Barèl performed data analysis until around 1996. BaseClear moved to a new facility at Leiden Bio Science Park in 2003. Three years later the company obtained an ISO 17025 accreditation for paternity testing. As time went on, BaseClear grew bigger and bigger and the building was getting cramped. A new one was designed and built at Leiden Bio Science Park and the move took place in 2018.
Latest Technology BaseClear invested in state of the art equipment from the beginning. Remarkably, Reichert and Barèl always invested their own money. Barèl: “We have never received any external investments and were able to use our earnings for investments. Also, we always made sure we had the latest technology in-house, even if this meant investing a lot of money in new machines, while we had just bought the second-last version.” BaseClear is now the biggest independent genome specialist in Europe. The company has more than sixty employees. As an independent business, it is much more flexible than companies with shareholders. This is one of the reasons that BaseClear is able to stay at the forefront of (technological) innovations.
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D Different Markets BaseClear has three business units that offer services for selected customer segments. Furthermore, there are four subsidiary companies, each with their own focus. Each business unit or subsidiary company creates added value related to a speciďŹ c product-market combination.
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The BiaNomics business unit focuses on microbial genomic research to assist with research and development projects of food and pharmaceutical companies. These companies use microorganisms in the production process, for example as fermentation model, or as part of the end product, as is the case with probiotics. Analysis of the genetic material of these microorganisms helps in ďŹ nding a mixture with desirable characteristics. The BiaNomics business unit also works on microbiome analysis and even cooperates in clinical trials. BaseClear also does a lot of work in quality control and quality assurance of production
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facilities, via the Quality Solutions business unit. Clients are mostly found amongst food and pharmaceutical companies. The business unit can identify microbial contaminations of a product, for example in spoiled food. Their work revolves around two questions: what kind of microorganism caused the contamination, and what was its source? Was it, for example, Salmonella originating from the hands of a production worker, or E. Coli from a pair of dirty shoes or some raw materials? To answer these questions, clients collect samples from various products and locations and send these to BaseClear for analysis.
And the third business unit, BaseClear for Academics, is geared towards the cooperation with academic partners, such as universities and research institutes like RIVM and TNO. These clients often have a lot of expertise in DNA analysis technology, but they do not have the equipment or employees to do the analysis themselves. Subsidiary Companies The services of subsidiary company ProBase Pharma are similar to those provided by the Quality Solutions business unit. However, the work of ProBase Pharma is compliant with good manufacturing practices (GMP) – international standards for quality control. Depending on the quality level that the client needs, they can select the services of ProBase Pharma or Quality Solutions. BaseGene is a subsidiary company
focused on gene synthesis. This company can make constructs which can be used for diverse applications. The kit that MyMicroZoo sells for the microbial analysis of the gut flora (see page 5), can also be used in clinical trials with medicines that work against a disease by improving the intestinal flora. Currently, BaseClear works together with academics and companies on a research model to test this type of medicines. Subsidiary company Future Genomics Technologies is a close collaboration between BaseClear and Leiden University. This company aims to translate the fundamental knowledge present at universities into commercial products faster. One recently finished project is the sequencing of the complete DNA of an orange tulip.
What kind of microorganism caused the contamination, and what was its source?
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Nucleus: The New Building BaseClear moved into its new building within the Leiden Bio Science Park in May 2018, only a stone’s throw away from the old premises. The new building is called Nucleus and with a surface of 2,800 square meters, it is twice as large as the one the company left behind.
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The design of the new building fulfils two aspirations of Reichert and Barèl: that it is beautiful, and that it is adjusted to the workflow. The building is very spacious and welcoming, with a central atrium where people can meet for lunch or a chat. The laboratory area is much larger and better organised now, so that it meets the even stricter demands for laboratories, with separate areas for different processes. Also, the design of the building facilitates efficient employee movement and waste streams. A dedicated lecture room for both internal and external meetings was also included.
Focus on Sustainability The new facility of BaseClear is the first building on the Leiden Bio Science Park with the BREAAM sustainability certification ‘Excellent’. This means that the building meets high standards regarding environmental, social and economic sustainability performance. “Our focus on sustainability is eminently logical for a company with many clients working in the field of biology”, Barèl explains. The label was obtained through, among others, the compact building volume, climate-control ceilings, LED lights and 150 square meters of solar panels on the roof.
Our focus on sustainability is eminently logical for a company with many clients working in the field of biology. BASECLEAR 25 YEARS
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F Future Technology The analysis of DNA is getting easier and less expensive. For BaseClear, this means that the challenges are shifting.
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The last twenty-five years have seen many developments in DNA analysis technology, and more change is forthcoming. The expectation is that in the not too distant future, it will be possible to connect a DNA sequencer to a smartphone, so people can perform DNA analysis at the kitchen table. Now that the analysis of genetic material is getting easier and less expensive, the challenges in the field are shifting. CEO Reichert explains: “When BaseClear started, about 80% of the operating expenses were for DNA analysis, whereas nowadays it is only 10%. Therefore, the focus is shifting to project set-up
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and data analysis. BaseClear is already active in these areas, and will expand its activities in the future.” Healthy Environment With regards to project set-up, BaseClear can advise clients about sampling, such as where to take samples and how many are needed. Advice can also include the most appropriate techniques for isolation of genetic material. One of the fields in which proper project set-up is crucial, is biomonitoring, the use of biological data to assess changes in the environment. For example,
The focus is shifting from DNA analysis to project set-up and data-analysis.
a healthy ditch ecosystem contains many different species. In the past, biologists had to go into the ďŹ eld with a landing net to catch the organisms, which was invasive and very time consuming. A new method uses environmental DNA to assess the diversity of organisms in water, which is based on the fact that animals that live in the water leave behind DNA via their faeces, urine or skin cells. Water samples from different locations therefore show local biodiversity. BaseClear cooperates with Leiden University and research institutes Naturalis and KWR in developing this method.
Handy Tools Another challenge in the ďŹ eld is data storage, management and analysis, since the amount of data generated has grown tremendously over the years and the analysis and interpretation is getting more and more challenging and time-consuming. A clear understanding of how the acquired data can be used is essential, and BaseClear helps by developing tools that can be used for data storage, statistical analysis, interpretation and visualisation. BaseClear offers these programs as SAAS, Software As A Service, which means that clients do not have to store the software on their own computers.
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C Marc Kolkman
Customer stories BaseClear’s customers can be found in Leiden Bio Science Park, elsewhere in the Netherlands, in Europe and beyond. Significantly, BaseClear is still serving many of its customers from twenty-five years ago.
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One of BaseClear’s first customers was Joop van Doorn, who worked in a laboratory for research on flower bulbs in 1993. He studied the DNA of bacteria that can infect hyacinths and regularly utilized the services of BaseClear. What he really appreciates about BaseClear’s approach, is that its employees are always willing to be creative and look for solutions. Van Doorn explains: “Sometimes, I wanted something different from the standard methods, for example different DNA solutions for use in the lab. Other times, I wanted to use new DNA sequencing techniques. As soon as I presented my need to BaseClear, they said they would try to find a way. Sometimes it would be quiet for a little while, but sooner or later
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they always contacted me to tell me there was a solution. They were also realistic in outlining the options and would be upfront if something was not possible.” Proactive stance Another customer of BaseClear is DuPont or, more specifically, its Division of Industrial Biosciences. The two companies collaborated on many projects involving the optimisation of various enzymes, for example those used in washing powders or that improve the production of bioethanol from corn. Marc Kolkman is staff scientist for the Dutch Division of Industrial Biosciences, which is located at Leiden Bio Science Park. He says: “BaseClear’s
Joop van Doorn
facility is literally just around the corner and we enjoy a pleasant working relationship. We have worked with them for about twenty-ďŹ ve years now and they know what is important to us. What I really like is how proactive BaseClear is: their people contact us when they have new technology which might be of interest to us. A good example is some of the latest sequencing technology, which is very suitable for analysing sequences of the large numbers of protein-engineered enzyme variants that we create and screen. I also really appreciate that we have developed customized bioinformatics tools together. These tools allow us to search for enzymes with desirable characteristics without having to do all the bioinformatics ourselves.“
We would like to congratulate BaseClear on their new building and their anniversary!
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Congratulations on 25 years of entrepreneurship
It’s in the genes! Oxford Nanopore congratulates BaseClear on their certification to provide high throughput, long-read, real time nanopore sequencing as a service. Learn more about Oxford Nanopore Technologies:
www.nanoporetech.com
An anniversary and a new location to accommodate the strategic ambitions, then you can say that undertaking is in the blood. Knowledge, expertise and excellent entrepreneurship. The big picture but also eye for the smallest details. That’s all in the profile of Bas and Erna. We are proud to be an eyewitness.
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Advertorial
Sustainability in Building The new BaseClear facility is the first on the Leiden BioScience Park with the BREAAM sustainability certification ‘Excellent’. Engineering firm Deerns handled the design of the installation and advised on issues related to building physics and sustainability.
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Since its founding 90 years ago, the mission of Deerns remained the same: Together we passionately create a positive impact on the built environment tailored to its users and future ready. All of Deerns’ projects are therefore characterized by their sustainable character. This mindset fits perfectly with BaseClear’s desire for a building which lived up to high sustainability standards. Measures A laboratory uses large amounts of energy and produces a lot of waste. In order to achieve the BREAAM sustainability certificate 'Excellent', measures were needed in many areas. The first step was a compact building volume, with a streamlined design characterized by friendly curves that turn into long, straight lines. The compact layout ensures short running lines and a limited use of materials. Other prominent choices are: connecting to the heat-cold storage of the Biopartner Foundation, an energyefficient installation system, LED lighting and approximately 150 square meters or solar panels on the roof. The office spaces in the building are equipped with motion sensors, so the lighting is only switched on when someone is present.
Interdisciplinary Approach The ambitious sustainability goals were only achievable through collaboration between BaseClear, Deerns, the architect and several other parties. Decisions had to be taken in many areas, which influenced each other and had to be coordinated and kept within budget. Since the work was performed directly for the end-user BaseClear, the focus could be on the total cost of ownership. The classic dichotomy between investment and exploitation burden was inconsequential. This made it easier to invest in economical techniques.
Fleminglaan 10 2289 CP Rijswijk Postbus 1211 2280 CE Rijswijk Tel +31 (0)88 374 0000 contact@deerns.com www.deerns.nl
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W Word of Thanks
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We at BaseClear are very proud of what we have built over the last twenty-five years. But as a service provider, we would not be here without our customers and collaborating partners. We are very grateful that we are still serving many of our customers from twenty-five years ago. It is a confirmation that we are doing the right thing. We also highly appreciate our pleasant cooperation with, among others, universities and research institutes. Due to our joined efforts, we were able to further improve our services and develop new products. We would also like to thank the architect, construction manager, contractor, and all other persons involved in designing and building our new facility. It was only through our fruitful collaboration that we were able to achieve
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our ambitious sustainability goals and we are very contented with the result. And of course, we would like to show our gratitude to our employees. Thank you all for your dedication and enthusiasm. The success of this company derives in in large part from your efforts. The last twenty-five years have seen many developments in DNA analysis technology, and it is a pleasure to see where we are right now. We are looking forward to the next twenty-five years and we would love to work together with our customers and collaborating parties to develop more services and products with positive impact on our society. Bas Reichert, CEO and founder Erna Barèl, COO and founder
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