The Unsung Lab Hero of the Human Genome Project

While National DNA Day, the annual event commemorating several major milestones in genomics discovery, may technically only be one day, its significance to genetic research is felt year-round. The event was originally established in 2003 to celebrate the completion of the Human Genome Project (HGP) in April of that year, an ambitious international effort to map and understand the human genome – all three billion base pairs.

Since its completion, this resource has been instrumental for genomic research, providing scientists and health care professionals with unprecedented visibility into the structure, organization and function of all of humanity’s genes. Equally as exceptional as the discoveries that this 15-year long effort uncovered, were the testing solutions and procedures conceived to carry out the project. We had the opportunity to hear about one such project from our very own Keith Whittlinger, a staff engineer within our laboratory products division, who was instrumental to the development of the world’s first commercially available 384-square well plate – now known as the Nunc® 384-Well Plate.

From the onset, researchers involved in the HGP knew it would be an arduous process, especially within the 15 -year timeframe. In order to complete their shared tasks within this period, participating organizations – including the DOE Human Genome Center at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), and Lawrence Berkeley National Laboratory (LBNL) – were aggressively pursuing collaborations for any consumables, technologies and instruments that could speed up the collection of cloned DNAs, synthetic DNA oligomers, DNA library production, and cosmid libraries and rearrying libraries for larger distribution.

However, in the early days of the HGP in 1992 and 1993, current efforts and capabilities for rearrying and distribution of libraries could not possibly match the demands of all the HGP sites. To address this need, Dr. Don Uber of Lawrence Berkeley National Laboratory, the engineer who developed the first robotic colony pickers, and Dr. Greg Lennon of Lawrence Livermore National Laboratory conceptualized a 384-well “waffle plate.”

The idea was daring to say the least, proposing a significant augmentation to the 96-well plates being used at the time. But the researchers were confident that this new system was necessary for completing the project within the allotted timeframe, as it would allow for a fivefold-deep, five-replicate set of each library.

The Nunc® 384-Well Plate was designed with the same length x width x height footprint as the commonly used 96-well plates, so researchers could seamlessly integrate the new plate into their workflow, while also exponentially increasing throughput. This increase in sample throughput was derived from the inclusion of four wells, which occupied the same dimensions as one well in a standard 96-well plate.

Additional benefits and capabilities of the new well design included:

The safe and secure optimization of freezer, incubator and work spaces as sample demands increased throughout the project.
A standard size well ideal for use with automation, including liquid dispensing instruments and colony pickers.
Compatibility with robotic and manual multi-channel pipettes as well as lids specifically designed to accommodate any robotic de-lidding that was being used with the 96-well plates.
Design features that provided secure stacking of the lidded plates.
C-well geometry design in each square well for enhanced growth, optimal reading of each cell, and strategically-designed curved corners for optimized sample volume and recovery.

Several years into the HGP, Dr. Greg Lennon was honored for his ongoing contributions at the 1997 Microplate Technology Conference. While his impact on the project goes beyond conceptualizing the 384-well plate, his presentation spotlighted the importance of this new tool in the completion of the genome map as well as its larger implications for ongoing genomic studies and multi-disciplinary research.

Although originally designed and developed for the HGP, the Nunc® 384-Well Plate quickly became an ideal format for cell-based assays, enzyme assays, High Throughput Screening (HTS) using robotics and many other applications.

While the success of the HGP is a direct result of the research team’s passion, determination and tireless efforts, it’s an honor to recognize and reflect on the role the Nunc® 384-Well Plate played in supporting these efforts. It is with great pride that we celebrate the ingenuity of the team involved in its creation, including those who continue the longstanding tradition of serving science here at Thermo Fisher Scientific today, and the incredible origin story of this essential lab product that continues to be an integral part of our product portfolio.

To learn more about the Nunc® 384-Well Plate, click here. For more information about Thermo Fisher Scientific’s suite of lab products and how we can support your next genomic discovery, visit our Genomics Workflow portal.