#core facility

Author: Gabor Bethlendy

I grew up in communist Hungary and moved to the United States with my family at the age of eight. How we got here is an interesting story better left for another article. The point is that most kids growing up in the US had chores like taking out garbage or mowing lawns. However, in Hungary my chore was to ride my bike to the only store in town and stand in the bread line, sometimes for hours. My reward for this was often a Coke I bought at the bar next door. The year was 1975 and for my brother and me  standing in a bread line was a normal part of life with hours spent trying to game the system to get the best bread. 

The Bread Problem

Hungary had lots of bakers, many really good. But the bread had to navigate a difficult path from the baker to my family’s tummies: Few trucks, poor storage, and too few stores to distribute.  There was too much bread for some areas and too little for others; many loafs grew stale or moldy or went wasted, uneaten. We never knew what we would find.  But often when I arrived to the front of the bread line I was amazed to find that the shelves were full!  How could this be when there seemed to be plenty of workers handing out bread? 

The Sequencing Problem

When we visit academic or commercial sequencing facilities we see the same issues. Plenty of lab technicians, plenty of instruments, unused machine time and plenty of empty, unused lanes on sequencing runs.  Yet in many labs, freezers are full of partially filled boxes of various types of prepped libraries…all waiting to get on one or another instrument at some yet to be determined date. Why is this?

This is genomics’ equivalent of the breadline, folks with advanced degrees waiting for data - science’s equivalent of bread - with little control over access or timing. What a waste…

It is somewhat ironic that after 40 years in the US I find myself starting a company focused on solving a distribution and access problem, not for bread but for genomics. Making bread and sequencing samples are actually very similar businesses and as such manifest very similar problems. Both are abundantly available, yet both resist the notion they are “commodities.” Both require a machine - an oven or a sequencer - a few simple ingredients and well-trained operators who all claim they are the best at sour dough or Chip Seq. However, being skilled in production doesn’t translate to matching market needs.  Nobody gains if the bread goes bad or the lane goes unused no matter how delicious the loaf or good the prepped library is.  

Meenta Solves Genomics’ Breadline Problem!

Cloud based solutions can put an end to Genomics Breadlines. No, we don’t mean a Google search that results in a list of service providers! Those lists are not actionable and don’t speed up or decrease the cost of science. We propose an app that will tell us the availability and status of every single scientific instrument (@MeentaNGS) in the world.  We mean shared access with the ability to book time on them! We mean optimizing machine utilization by matching samples to available machine time throughout the world. Until then we will have to know by tribal knowledge which shops have good bread and which good library preps. With our app one can identify the good bread without the lines!

Author: Gabor Bethlendy

Below are the top reasons. If you think they have merit then read further.

1. Reagent “discount” economics don’t add up.

2. There are already too many next generation sequencers (NGSs) in the world already, and buying another under-utilized sequencer is a business model that favors the NGS manufacturers, not the facilities who use them.

3. More instruments does not equate with more access.

Let’s start with #1: Reagent “discount” economics don’t add up

First, the high price of, and poor access to, NGSs combine to drive up their service fees.  Second, the full price of the instruments is being amortized across the life of the instrument (typically three years)—when only 48% of its capacity is being used during this period (48% is the median utilization rate)! These amortization costs are also wrapped into genomic service fees.  

So what do the clever sequencing vendors do?  They offer you a second or third sequencer for a large reagent discount arguing this will bring down your per sample cost and hence the cost of your services when in reality all of those costs have already been captured in their calculation of the instrument price itself!

This is a false economy, or put more simply, there’s no such thing as a free lunch…

Which leads to my next point…

#2  There is already too much sequencing capacity, and more sequencers merely serves the NGS vendor’s interests

According to the latest figures, Illumina accounted for nearly 80% of the market share of next generation sequencers and about 4,800 instruments globally. By my calculations, this is >1 peta base-pairs of global capacity (to keep the argument simple, we’ll ignore the other NGS providers like Life Tech, Pac Bio and Oxford).

This is enough to sequence about 1 million genomes at 30x coverage on one of the Hi Seq instruments.   At the moment there are nowhere near 1 million genomes being sequenced each year and genome sequencing only represents a small (~10%) fraction of the NGS use case.  So why are institutions buying more of them?

One reason may be the above-mentioned 48% median instrument utilization rate. So while theoretical capacity may be high, demand out strips capacity due to poor instrument utilization.

Figure: Worldwide sequencing overcapacity is reaching ridiculous levels

We are often lead to believe that core facilities and sequencers are “busy” because we hear (or experience first hand) how long it takes to get on an instrument and get data back.  The erroneous conclusion we reach is to buy more sequencers to get better access, faster access or better data quality.

This is not the full picture. Yes, we often hear core facility managers argue that this is because NGS is a “very complex” workflow or that it is “not a commodity” and therefore difficult to scale up.  And while I agree in part, the fact is that academic and even many commercial labs are very bad at making full use of the sequencers they already have.  Either they don’t have enough business or more likely that their mission is to make discoveries not to make things more efficient. 

However, these are all truisms that distract us from the huge problem of poor access to expensive capital equipment in all of Life Sciences! The problems are efficiency and access.  And, the fact that these concepts aren’t as a sexy as that paper in Nature or Science is used to full advantage by the sequencing vendors; they are quite happy with the status quo as it keeps us naive scientists writing grants with taxpayer dollars merely to improve NGS vendor profits.  

Which leads me to the last main reason not to buy another sequencer…

#3: It’s all about sequencing access!

By having us buy more instruments for a larger reagent discount the vendor has done a Jedi mind trick on an entire industry all to give us “better access” and “some savings.” And as we discussed above, this is a false economy.

So, is the main problem the cost of sequencing or better access?  

I know many of you would say; “but I have a core or I send my samples to a collaborator or I search Google” and it’s easy for me to get on a sequencer.  And I think this is what most people said before Uber and ZipCar…that it is easy to hail a taxi as they are all over the city.  Yet, today Boston alone has about 40,000 Ubers (not to mention Lyft) circling the city on a daily basis!  How is this possible when there are enough cars and public transportation available already?  

Uber and ZipCar have lead consumers to an important understanding…for most, transportation is a service, and like many services these days, it is often less expensive and more convenient to rent it when we need it.

I am an American, and having my own car was really tied into my notion of American freedom and independence. But there is one thing I am even more attached to—my money.  That and anything that can lead to less headaches or more time in my life.  The convenience of ordering (and not owning) transportation has certainly helped in this regard.

Today, in the Life Sciences we are just like many car owners before Uber and ZipCar…we do not yet appreciate how difficult it is to get access to sequencers and other instrumentation…nor do envision how convenient it can be!

We have accepted the pain of how it is today.  

We have accepted that we send it to the local core or our favorite service provider.

So here’s my question: Assuming quality were the same, would you care which sequencer access you use? One selected through an Airbnb-like application or would you rather wait for your “favorite” one like you do today?

Since some of the sciblr folks are early-career or aspiring STEM researchers, I thought I’d talk about the place I work, and explain that little piece of How Science Gets Done. As someone who came to this from a working-class non-technical family, I didn’t know how any of this stuff happened or who to talk to, and I missed out on tons of resources as a result.

So! I work in a core facility, which is one type of lab where research can be done. Labs come in a few different types.

-There are classroom labs, designed for the maximum number of students to get hands-on experience at once. It’s not common for them to be used for actual independent research, unless a professor has structured her class in a way that produces some data, or has some unusual-for-her project that requires really common equipment that she doesn’t normally need.

-There are labs that belong to one, or a very small number, of professors. If you do an independent research project or “join a lab”, this is probably where you’ll spend most of your time. The prof has purchased equipment, chemicals, etc, for that lab, and he’s probably carefully spent that money on things that align closely with his projects, that his students will use frequently, and that he wants a lot of control over. But there are downsides to buying stuff for your own lab. It’s like buying books (I’m talking experimental research, here, so assume paper books for the analogy to hold). Books look nice, and are nice to learn from, but they take up space, and they cost money, and their resale value is minimal. And if you let your students loose among them, they may spill some toluene in them and put them back and never tell you until you use them again and ARGH anyways.

But what if you need that equipment once a year and it takes up a ton of space? What if it’s a new shiny toy and you don’t have a million dollars to blow on it, just to find out it’s not that useful? That’s where core facilities come in.

-Core facilities are shared labs, a little like a library for instrumentation. Someone else maintains the equipment (hopefully), and either trains all comers on the equipment, or takes in samples and sends you data. Unlike a library, usually need to pay--either by the hour, or by the sample, or by the day of usage. The charges cover some of the costs to run the instruments, pay the staff, buy consumable supplies, etc, but it usually doesn’t cover all of it. The rest is covered by grants*, gifts, or professors chipping in to pay extra for something that’s important to them, but not enough to pay for *all* of. Core facilities usually have really expensive equipment, and staff that are very knowledgeable about operating the equipment.

Core facility staff, like me? Our whole job is to help researchers. We usually expect that you are not the expert on the equipment you’re about to use. We usually don’t expect you to know the first thing about it! It’s okay to say “My prof asked me to use this. Why?” or “Hey, I think this would answer my research question, can you help me figure out if that’s the case?” Meeting with students to talk about their research project is about 20% of what I do, and I always feel bad when someone has clearly been floundering for a while before contacting me.

We’re not here to do all your work FOR you. Sometimes I do have researchers who expect us to run their samples for them (fine, for the stated per-hour cost), and do some analysis (fine, for an additional cost), and research their specific project or write a report of the findings (not fine, especially for students). But that’s rare. Mostly our job is to help, and we probably know more about the techniques we specialize in than your prof, and have more free time too. Ask us stuff! We like to talk. As this wall of text indicates.

Core Facility Advertisement complete. Want to see what resources your university has? Search for core facilities and see what’s there. Different universities arrange their cores differently; some are all under one umbrella but most operate pretty independently. Schools focused on undergrad education will probably have fewer resources on this front, but even they are likely to have some shared instrumentation funded by individual departments.