Going Green: How Research Labs Can Become More Sustainable

On By Adam LynchIn MiscellaneousLeave a comment

Hello Lab Notes readers! Can you believe it has been 7 months since the last blog piece? 2020 has been a challenging year to say the least with COVID-19 still spreading across the country. All of this to say that after a long hiatus, Lab Notes is back. In this piece we are talking about sustainability and waste in the research industry, and how research labs can reduce their carbon footprint.

Academic research centers, Biotech, and pharmaceutical companies work to discover and develop new technologies, medicines, and products that are essential to our daily lives. Often lost in this process is an awareness for more environmentally sustainable practices. On average, research labs consume 5x more energy and 4x more water than typical offices and consume an estimated 5.5 million tons of plastic each year (6,7).

In this blog we will see why research labs utilize so much single-use plastics, consume so much water, and energy-intensive equipment, and some ways they can reduce their carbon footprints. The research industry is about half the size of the automotive industry and thus, provides a big opportunity to become more sustainable.

Scientists are high-volume users of single use-plastics. Gloves, assay plates, petri dishes, conical tubes, pipettes tips, vials are just a few examples of common single-use plastics. Plastics are a convenient option for the research industry. Their single use allows for easier and effective sterile practices. They are also easy to produce and distribute. Plastics allow for easier transportation of biological samples and can both be used and disposed of in large quantities. These plastics can help researchers perform a number of experimental procedures: culture cells/bacteria, extract DNA and proteins, store/preserve samples, add reagents for a readout. The use of chemical reagents and biological samples can be dangerous to human health/safety if not disposed of properly. Hazardous waste cannot be recycled so it undergoes different treatment options: incineration, autoclave, microwave, or chemical treatment.

One solution to reducing plastic consumption might be a return to glassware. Before the development of plastics for research purposes, glassware was used for the same purposes. Recycling is another effective way to reduce plastic waste. Manufacturers have developed waste management systems and take-back programs to recycle lab plastics. Styrofoam coolers, gloves, pipette boxes, certain reagent bottles, conical tubes and more can all be recycled; the key is setting up an effective system in the lab to separate waste from recyclable materials. Viewing laboratory supplies as permanent, and not consumables can save overhead costs on single use consumables and promote sustainable practices.

Water is also essential to lab operations: it is required to: maintain health/safety standards of researchers (washing hands), fill incubators that house cells, water baths to heat reagents, Sonicators, autoclaves, and other lab experiments. Unlike plastics, water consumption can be harder to monitor. There are some easy solutions to reduce unnecessary water usage in a research lab. Distilled water is a more purified water used for lab experiments and cannot be replaced by tap water. Using it only for it is intended use can go a long way, considering it takes nearly three gallons of water to produce one gallon of distilled water. Autoclaves are commonly used to sterilize glassware and reusable lab plastics. Autoclaves require large amounts of cold water to cool down the hot water that drains from the system after each use (single pass system). By putting them on a closed looped system (recirculating), up to 70% of water can be reduced.

Next, energy conservation is a concept we are all familiar with. In our personal lives we are encouraged to make conscious choices to reduce wasted energy, such as using energy efficient appliances and turning off unused appliances. Research labs are one of the largest energy-consuming industries in the country (3). This is due to the large number of energy intensive pieces of equipment that, in some cases, run 24 hours a day. Ultra-low temperature freezers that store biological samples and reagents at a temperature of -80°C for later use, are a prime example. Interestingly, one -80°C freezer can use as much energy as an average household every day. Simply reducing the temperature to -70°C can reduce energy consumption by 30-40% while still protecting biological samples for later use.

Another important piece of lab equipment, water baths, can consume as much energy as a dishwasher every hour. Large water baths can consume as much energy as a window air conditioner every hour. Tissue culture hoods with frequent usage can consume about half as much energy as a house (7).The lesson here is similar to our daily lives, turn off non-essential equipment when not in use.

Finally, sustainable procurement practices are an often over-looked but important action to reduce a lab’s carbon footprint. While writing this piece, I was pleasantly surprised to learn how scientific vendors are addressing environmental sustainability. Creating high quality products with less plastic and creating take-back programs are good initial steps to reduce plastic waste. Organizations such as My Green Lab have been created to provide support to research labs/facilities as they try to reduce their environmental impact of their work. On top of identifying solutions like the ones discussed in this blog, My Green Lab provides support for labs looking for sustainable product recommendations. In order to do this, they have created a label called ACT (accountability, consistency, and transparency) that contains data about the sustainable features of a given lab product. Over time they hope to catalog hundreds of sustainable products to help the research industry become more environmentally sustainable.

I think most scientists are somewhat aware of the high-volume usage of plastics, water, and electricity needed to produce high quality research on a daily basis. But what is not often is realized are the necessary solutions or steps to reduce our carbon footprint. Throughout this blog, we have seen examples of how scientists can make smart sustainable choices. Whether you work in a research setting or not I hope this piece will help inspire you think about ways to be more environmentally conscious in your daily life.

References:

  1. Bell, Alice. Can Laboratories Curb Their Addiction to Plastic? 10 Nov. 2019, http://www.theguardian.com/environment/2019/nov/10/research-labs-plastic-waste.
  2. May, Mike. The –80 Takedown. 2 Oct. 2017, http://www.labcompare.com/342365-The-80-Takedown/.
  3. Paradise, Allison. A Greater, Greener Commitment. 2016, http://www.labmanager.com/business-management/a-greater-greener-commitment-4957.
  4. Paradise, Allison. Taking ACTion on Sustainable Purchases in the Lab. Dec. 2018, blog.quartzy.com/taking-action-on-sustainable-purchases-in-the-lab.
  5. Relph, Rachael. Making Sustainable Labs a Reality. Apr. 2020, http://www.labmanager.com/business-management/making-sustainable-labs-a-reality-22090.
  6. Urbina, M. A., Watts, A. J., & Reardon, E. E. (2015). Labs should cut plastic waste too. Nature, 528(7583), 479-479.
  7. http://www.mygreenlab.org/about.html.

From Bench to Bedside Part 1: Discovery

On By Adam LynchIn Drug DevelopmentLeave a comment

Translational research is a humbling process. It is about turning a scientific idea into a treatment that will hopefully one day change the lives of real patients. It’s almost two years since I started working for Remedy Plan Therapeutics. From day one, there have been some really big questions thrown my way. Friends, family and colleagues all want to know how a new cancer drug is discovered and most importantly when it will reach the clinic. I love these big picture questions, and I appreciate when people ask them. Cancer is so deeply rooted in our culture; we all probably know someone who has been affected by this pervasive disease. With that in mind, who wouldn’t be excited about a new approach to treating cancer in the near future? In a special Bench to Bedside series, my goal is to share with you an overview of the drug development process, in a way that is simple and easy to digest. This first post will describe step one of the process: drug discovery.

Drug discovery like other forms of research, follows the scientific method throughout each stage. The first step is a clinical need or some sort of observation. Scientists and researchers look at clinical trends and start to ask questions: why haven’t there been considerable improvements in treating cancer? What makes cancer so hard to treat? There are a seemingly infinite number of questions that are generated.

In response, researchers investigate data generated by their colleagues in order to see what approaches have been previously tested and what the results of those experiments were. Based upon the findings of previous studies, new hypotheses start to form. For example: “inhibiting protein ‘X’ in pathway ‘Z’ might lead to therapeutic effect in cancer type ‘Y’. The subsequent big picture goals are to identify drugs that when treated produce the desired biological response on the bio marker/target (in this example inhibiting protein ‘x’). Before a drug can be discovered, we need to be sure that the activity protein ‘x’ is a suitable indicator for measuring a therapeutic response. In order to test this initial hypothesis, scientists develop a series of experiments to both test and validate the activity of the bio marker of interest within the context of the disease (cancer type).

High throughput screening (HTS) is a method used to test thousands of ‘druggable’ molecules (usually small synthetic molecules) against the activity of the selected biological target. These small molecules may be commercially available for researchers from a variety of scientific disciplines to test against their target in order to identify a biological or therapeutic response to a particular disease (these are referred to as ‘hits’).

At Remedy Plan Therapeutics, we use our novel platform (technology) to measure embryonic-like properties in cancer cells (cancer stem cells).  These embryonic-like properties in cancer cells are what make cancer so hard to treat; they help cancer cells to continue to grow, spread and potentially develop resistance to current treatments. When we screen thousands of small molecules, we are testing them against our biological target in order to identify hits that lower these embryonic properties in cancer cells. At the end of the high throughput screen, we analyze data from thousands of potential therapeutic drugs and identify hundreds of initial hits that lower some of the most dangerous properties in cancer cells! This is really exciting, but all great results must be reproducible. In order to rule out false positives, the original high throughput assay or experiment is re-run in order to reconfirm the biological activity of selected hits.

Another important aspect of validation might involve designing experiments to measure off-target effects of each ‘hit’. An off-target effect is when a drug binds to different cellular targets than were originally intended to. This could potentially lead to unexpected side effects that may be harmful. It can take a matter of years to reach this point, where thousands of potential drugs filter into a handful of lead candidates to build a drug development program around. The discovery process is, of course, just the beginning of a long road from the laboratory bench to a patient’s bedside. The next Lab Notes piece focuses on the lead development phase. It’s during this stage that new cancer drugs are characterized further both biologically (in-vitro studies) and chemically (lead optimization).

General overview of the various components of drug development

Featured Image Cited: Fleming, N. (2018). How artificial intelligence is changing drug discovery. Nature, 557(7706), S55-S55.

New Heights

On By Adam LynchIn Startup Life4 Comments

Startup life is unique; it is a fast-paced work environment that requires team members to wear ‘multiple hats’ in order to hit major scientific milestones. It’s been a busy summer at Remedy Plan Therapeutics; with our expanding scientific operations we have been generating a lot of exciting data to advance our research and discovery efforts. In the process, we moved out of the old ‘garage lab’ and into a more spacious facility geared towards the growing biotech scene!

Greg Crimmins, CEO & Founder of Remedy Plan Therapeutics (top left)
The new lab fully stocked and ready for experiments, Gaithersburg MD (bottom left)
Dennise A. De Jesús-Díaz, Vice President- Scientific Operations of Remedy Plan Therapeutics (right)

Our new building fosters a collaborative environment where scientists from different biotech companies can network and share scientific equipment. In order to properly celebrate the new lab, we recently hosted an open house. Open houses are great, they provide researchers the opportunity to interact with all the people who have made our scientific progress possible. There was an incredibly diverse group of people present: friends, family members, scientific partners, and investors.

So, what is it like to give a lab tour to such a diverse group of people? Communicating science is nothing new for researchers, a big part of our job involves sharing ideas and results among colleagues. However, interacting with investors and other business entrepreneurs is a pretty unique experience. Stepping into a lab can be a bit overwhelming– there are rows of bench-tops filled with equipment and consumable materials. Generally speaking, people are not just interested in learning about what these scientific devices do, but also where they fit into the overall scientific operations. This piece is about sharing a scientific story through a virtual lab tour.

Station 1: Growing, counting, and plating cells

|Tissue culture room| |Hemocytometer| |Automated cell counter|

The tissue culture room is the dedicated space for cell based experiments. Here, Remedy Plan researchers grow and maintain cancer cells in a sterile environment for experimental testing. Performing these experiments allows us to characterize our compounds (potency, mechanism of action, cell death) for clinical decisions. If we want to perform a cell based experiment we must first prepare a solution of cells before transferring them to an assay plate which house each sample. There are a couple of different ways to do this. The first is to use a hemocytometer, a device invented in the 19th century to perform blood counts. It consists of a glass microscope slide with a grid of perpendicular lines etched in the middle. The grid has specified dimensions so that the area covered by the lines is known, which makes it possible to count the number of cells in a specific volume of solution. The second method is a lot easier; it involves using an automated cell counter. This device is able to accurately count cells in a given population based upon size. The average diameter of a Eukaryotic cell is about 10 micrometers, things that are either much smaller or larger than this are excluded.

Station 2: Testing potential drug candidates

|Chemistry Station | | HP D300 | | Luminometer |

The next series of scientific stations demonstrate how Remedy Plan researchers transition from experimental design to actually obtaining experimental results. The chemistry station is where compounds transition from design to testing. Here we measure the powdered stock of the compounds in order to dissolve and prepare stock solutions for in-vitro (test tube) testing. In order to physically test our compounds, we use a machine (HP D300) that uses the same technology as a printer. Instead of dispensing ink blots in precise locations we dispense cancer drugs (thanks for the inspiration Harvard ICCB Lab). Depending on the biological or chemical property that we interested in measuring, we might use a luminometer to quantify values such as luminescence (light). Reagents are added to drug treated cancer cells that convert a chemical reaction into light which we can analyze.

Station 3: Measuring Genetic Markers:

| Quantitative PCR | | Thermocycler | | Nanodrop |

The genetics area pictured above is my favorite part of the lab. We use the equipment above to determine how effective our therapeutic compounds are at altering specific genetic markers. In order to this DNA/RNA must first be extracted from cancer cells. We use the nanodrop spectrophotometer to quantify this with just 1 microliter of sample! To actually measure genetic changes, we use a technique called polymerase chain reaction or PCR for short. The goal of PCR is to experimentally perform the processes that allow cells to be copied or replicated prior to cell division in controlled laboratory conditions. Samples containing the DNA mixture of interest are put into the thermocycler machine, which regulates the different temperatures needed at each step of the process. This technique enables scientists to produce millions of copies of a specific DNA sequence from a small sample – sometimes even a single copy. By amplifying DNA over and over again via qPCR machine we can measure gene expression levels in response to drug treatment over time.

Giving a lab tour, especially to non-scientists, is fun and exciting. Business entrepreneurs and investors tend to ask really great big picture questions. Other non-scientists love hearing about cells, how we grow them, and how the lab equipment can measure such tiny things with accuracy.  Showing a lab is like sharing a scientific story– a story where big ideas like developing cancer containment therapy inspires curiosity, which drives really big questions, which in turn drives important experiments that are performed in the lab by very motivated researchers. For me personally, events like this leave me with a sense of gratitude.  It’s really great to share all of the hard work and progress that goes into research and discovery with other people as our team moves forward towards getting into the clinic!

The Power of Automation: How Robots Can Help Researchers Fight Cancer

On By Adam LynchIn AutomationLeave a comment

When I first started working in biotech, I had just joined a small cancer therapeutics startup. Our old building had bad ventilation, undrinkable water, exposed ceiling areas, and periodic leaks from the ceiling. This was incredibly exciting: to me this was the stuff of startup legend. Three scientists working in a “garage like” atmosphere to develop a new cancer therapeutic! Part of my initial training was dedicated to learning our novel screening platform, which allows us to identify compounds that target metastatic properties of cancer cells. I didn’t realize it at the time, but my entire understanding of science & technology was about to change. Startups have to be creative with limited funding/capital. Scientific equipment and reagents tend to be expensive on top of renting a space. With that in mind, there are just some experiments that you can’t do from a “garage”. Within a month after starting this new job I spent 4 months working at Harvard Medical School’s ICCB lab; a world class screening facility that uses automation to help drive research and discovery.

The old Remedy Plan headquarters. The “big” lab served as the office (3 desks), an impromptu meeting room, and the lab for bench top experiments (left). The “small” lab was our tissue culture room where we performed experiments with cells (right).

Working at Harvard, I learned how to use some really cool robots to perform large scale experiments. It was there that I came to realize that the actual methodology of molecular biology is simply moving incredibly small volumes of liquid from one place to another. This is an oversimplification of course there is a lot of complicated science that goes into those liquids. But regardless, a very large number of very small volumes of liquid need to be transferred from one place to another to conduct our experiments. The robots at the Harvard lab allowed us to do this via high-throughput screening, which is a method of testing a lot things (in our case small molecule libraries) in a short amount of time.

Pipetting tiny volumes of liquid by hand with precision and accuracy is a vital part of obtaining good data. Liquid handling on a large scale can be extremely monotonous and time consuming, leading to fatigue and therefore mistakes. With that in mind, automation is an incredibly powerful and necessary tool for research & discovery! Introducing robotics to the laboratory is a good way to increase both the number and the accuracy of experiments performed; good science also means low variability between samples and reproducibility from peers. These characteristics save researchers from long, repetitive, laborious tasks and free up time for more important tasks like data analysis or deep thought or writing a blog…. My goal is to share with you a few robots that I have used to help accelerate our research & discovery efforts.

Cells are grown in tissue treated culture flasks and are transferred to an assay plate (384 well plate above) which houses each individual sample.
Video filmed with permission at Harvard Medical School ICCB Facility

  Let’s imagine we are running an experiment to test how effective a series of different drugs are at killing cancer cells. The first step is to transfer the cells grown in culture to a plate with individual wells (samples). The photo on above depicts a plate with 384 wells, that’s a lot of samples! If I wanted to add 10,000 cancer cells per well (3,840,000 total cells for just 1 plate) I would need to dispense 50 microliters of a solution by hand 384 times. This not only takes a lot of time but also requires steady hands since each well is less than a millimeter wide! The first robot (above) I learned how to use at Harvard can do this in less than 15 seconds by pumping a solution full of cells into a dispense head perfectly aligned with the plate. video on right courtesy of Remedy Plan Therapeutics.

Compound libraries (above) consist of molecules designed by chemists, each with unique properties that can be tested by scientists in multiple areas of research.

Janzen, W. P. (2014). Screening technologies for small molecule discovery: the state of the art. Chemistry & Biology, 21(9), 1162-1170.
The robot above is designed specifically to transfer these compounds from their library plates to our experimental plates filled with cancer cells.

Video filmed with permission at Harvard Medical School ICCB facility

Scale becomes a major deciding factor of what kind of automation to use. If we want to test over 8,000 small molecules at a time, we would need a lot of plates. We don’t have the ability to do this in our lab but facilities like Harvard are designed for this. Compound libraries (above) consist of molecules designed by chemists, each with unique properties that can be tested by scientists in multiple areas of research. The robot above is designed specifically to transfer these compounds from their library plates to our experimental plates filled with cancer cells. It takes the robot about an hour to do this at this scale, I can’t even imagine how many hours it would take me to do this by hand…

The final robot is my favorite, it was so vital to our screening efforts at Harvard that we decided to purchase one for our own lab. The D300 is a liquid dispensing printer, which uses the same basic technology as a regular printer. Instead of dispensing ink blots in precise locations, we can dispense different concentrations/volumes of potential cancer therapeutic drugs into wells filled with cancer cells. In a way, we are printing molecules! Unlike the previous robots, we use this machine in our lab on a regular basis to test optimized drugs to find a lead candidate for a clinical trial.

Automation is a powerful tool; it’s becoming more common in our everyday lives both inside and out of the lab to make ordinary tasks easier. Research is expensive: pricey equipment and labor costs mean scientists have to prioritize the experiments they think will give them the most information about the questions they are after, rather than performing all the experiments they would like. With the help of some incredibly clever machines, we can perform large scale experiments that bring us closer to our goal of bringing a new cancer therapeutic to a clinical trial.

Building Blocks

On By Adam LynchIn Cell CultureLeave a comment

I am a research technician at a startup biotech company; simply put, my job is to perform cell and molecular biology experiments that will help advance our drug discovery efforts (for more information view
https://remedyplan.com/science). Most of my time in the lab revolves around one very important technique that serves as the foundation for the majority of our scientific experiments: -cell culture! Cell based experiments are a great model system in drug discovery. In our case, cancer cells are perfect test subjects to identify compounds that lower embryonic properties without producing toxic effects. Scientists have been culturing (growing) cells for decades, and it has revolutionized the fields of cellular and molecular biology. Here is a glimpse into the science behind cell culture and how we use these principles in our lab to run experiments.

Cells are grown in tissue treated culture flasks. Each flask contains growth media (red) thatprovides the necessary nutrients for cells to grow/expand to the size of the flask. Temperature & gas exchange are auto-regulated by the incubator (“Selecting the Right Cell Culture Media.” Lab Manager, 9 Feb. 2017).

In order to cultivate cells in the lab we need to recreate the proper environmental conditions and nutrients that they would normally receive from their original source. First, we need to create the right recipe for growth. Generally speaking, the perfect cocktail consists of a combination of amino acids, carbohydrates, vitamins, and growth factors …Yum. Many cultured cells will only survive and proliferate when they are firmly anchored to their surroundings, as they would be inside the body. In order to accomplish this, cells are grown in ‘culture flasks’ that are coated with a material that allow the cells to attach to bottom of the flask and further expand. One of the realizations that I’ve come to is that growing cells is similar to growing plants; if given the appropriate nutrients, space, and environmental stimuli they will flourish. When house plants out-grow their containers they both run out of space & nutrients necessary to live. The same principle is true for cells. When they fill the space of the culture flask, we transfer a portion of the original population into a new flask with fresh growth media; similar to transferring a plant into a larger pot with fresh soil. This is called passaging cells.

The lifespan of most cells is genetically determined. They undergo the process of senescence (aging) and stop dividing after a certain number of cell divisions. Cell division serves not only to generate new cells, it allows for cell repair. Each division chops off the end of our chromosomes (telomeres) meaning they become shorter over time, this is thought to be the process that drives aging. Cancer cells have been altered to become immortal by expressing a gene called telomerase. This gene protects chromosomes from degrading, allowing the cells to keep actively dividing. Because cancer cells are immortal, if we continue to provide all the necessary conditions, we can passage cells in our lab indefinitely, ensuring that we always have enough cells to perform our experiments.

Looking back on my training I still remember the original sense of awe and amazement that comes with working with human cells. Cells are the building blocks of life. They provide our genetic blue prints and together compose the tissue and organ structures of our bodies. It never ceases to amazing me that over the years we have mastered the ability to extract these cells, grow them, and design elaborate experiments in order to tackle some of the greatest medical challenges of our time!

Hello World!

On By Adam LynchIn Miscellaneous2 Comments

Good company in a journey makes the way seem shorter. — Izaak Walton

 

My interest in science has always been intertwined with the relationship between how research & technology translate into medical discoveries. At an early age I gained exposure to the crippling effects of healthcare systems that are deprived of funding for medical research and basic resources upon visitation of my mother’s home country of Mauritius. This experience has served as a motivating force to pursue a career in research. My scientific career started as an undergraduate research student. I spent two years as a research assistant in a lab that utilized CAR T cells (Chimeric antigen receptors) that expressed a genetically engineered PD-1 receptor as a potential immunotherapy to target specific cancer cell populations. I went on to receive my master’s degree studying the effects of antihistaminergic compounds on metabolic phenotypes. I am currently a research technician at Remedy Plan Therapeutics.

I am passionate about research & discovery that is both creative and inspiring. I created Lab notes to share my perspective of what it is like to work in a startup atmosphere & provide a glimpse of the laboratory science that drives research and discovery. My journey in a startup has taken me to incredible places and has provided the opportunity to grow and develop as a scientist. In my first year I’ve played a role drug discovery via high-throughput screening and lead optimization. I’ve always felt that one of the most rewarding aspects of science is sharing the process & story with other people. Through this blog I hope to share with you a glimpse of not only what it is like to do science but how science and research transition from bench to bedside.

So, share your questions, and don’t forget to subscribe!

-Adam