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Medicine's Version of Santa's Workshop: A Laboratory Medicine Q&A

Published on December 10, 2015 in Cornerstone Blog · Last updated 4 months ago


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Laboratory medicine specialists in pediatrics have a lot in common with Santa’s elves. They are less visible and receive far less of children’s attention than the ones who directly deliver gifts or bedside care, but their behind-the-scenes contributions are essential for the whole enterprise to function correctly. Just think how often you and your family members of any age need to have blood drawn and wait for lab test results to receive the doctor’s diagnosis or a treatment decision.

Michael J. Bennett, PhD, FRCPath, FACB, chief of laboratory medicine at The Children’s Hospital of Philadelphia, is at the forefront of the professional group representing these essential experts in analyzing blood, tissue, chemicals, and cells. Dr. Bennett will serve on the board of the American Association for Clinical Chemistry (AACC) beginning in January 2016 as president-elect, then in 2017 as AACC president.

On the occasion of this new leadership role, Cornerstone sat down with Dr. Bennett, who is director of the Michael J. Palmieri Metabolic Laboratory at CHOP and a professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania to discuss his insights from 40 years of experience in clinical chemistry in pediatrics. The edited conversation about the importance of laboratory medicine and how the profession has advanced medicine through discovery, follows below.

What is exciting in laboratory medicine for you, particularly working in a children’s hospital?

Some of the challenges that we have in our labs are related to dealing with children being so small in size. When you and I go for a blood draw, they may take five or six big tubes of blood; you can’t do that with children. I’ve spent much of my career developing tests that use less volume to the point where there are tests now we can agitate on a blood spot that is literally just a drop of blood. We can actually get useful results out of that. I find that’s fascinating.

Another fascinating aspect of this work is in understanding some different diseases that children have. I’ve developed an interest in metabolic diseases. In addition to being the chief of laboratory medicine here at CHOP, I am the director of the metabolic disease lab. CHOP is one of only a few tertiary care hospitals in the unique situation of seeing a number of children with quite rare diseases with very major potential impact in terms of mortality and morbidity. We’ve developed the methods to diagnose these conditions.

I specialize in diseases of the mitochondria. In these conditions, you cannot get energy from fat. When you and I are fasting, we can burn our fat reserves to get energy. These children can’t do that. So if they have a gastrointestinal or vomiting illness, they’re losing calories, and they can’t replace those calories from reserves like the rest of us can. Over my career we’ve defined probably about 20 different diseases. I find that exciting as well because we’re not done yet. We’re still identifying new conditions.

Some of our readers may have observed that Pathology and Laboratory Medicine is the source of many basic science discoveries at CHOP and Penn. But much of what your department handles is highly clinical as well. Can you discuss this interplay of basic and clinical realms in laboratory medicine?

Much of the work that we do is clinical. Probably about 70 percent of clinical decisions are made as a result of a lab test of some sort. And we have treatments for some of these conditions and need to monitor those treatments. We are very busy turning out that clinical data for clinicians.

But, here at CHOP, we’re at the cutting edge of basic science as well. One of my roles here is to develop novel biomarkers for diseases. I do work with a very rare progressive neurodegenerative disease in children, juvenile Batten disease (JNCL). We are researching potential therapies for this disease, and we’ve been looking for biomarkers to help diagnose it earlier.

Unlike the form of Batten disease that had a recent gene-therapy advance at CHOP in dogs (LINCL), juvenile Batten disease is unlikely ever to be in the gene therapy arena, because the missing protein that’s causing this form of disease is actually bound to the membranes. No one has yet been able to insert a membrane protein through gene therapy. So for JNCL we’re trying to find other molecules that largely affect this protein’s action to prevent the brain cells from dying. We’ve been able to make an impact on cells in culture, and we’re currently working on a small worm model for this disease.

We’ve actually increased the lifespan of this worm. The worm with the disease dies after eight days as opposed to a normal lifespan of 14 days, and now we’ve got the worm up to about 12 days. Its lifespan is not completely normal yet, but we’ve had a huge impact on the worm.

What do you hope to accomplish in your new leadership roles in the AACC?

Prior to becoming president-elect of the organization, I was chair of their pediatric division, which is a division of members who work in children’s hospitals. I was also the contact with the National Children’s Study (NCS). Unfortunately, the National Children’s Study lost its funding, but for a long period of time I would advise the NCS on how to collect and use samples from what would have been the 21-year cohort of children in the study.

A big initiative I’m involved with in the AACC now is trying to develop normal ranges in children. We had previously used some of the NCS samples to begin this process. There are going to be many hospitals involved in this initiative, including many of the big reference hospitals such as ARUP, which is the reference lab we use here for tests that we don’t do in-house. We’re building collaborations with lots of different groups.

What we do is we take our population of many, many thousands of samples from many, many thousands of children, and hope that, after excluding outliers on either side because they’re sick, that the dataset in the middle, which is the bulk of the dataset, represents normal. Because we just can’t do it any other way. There is no way an IRB (Institutional Review Board) should or would approve drawing blood from normal kids just to do that sort of exercise.

The project is complex because in the pediatric population you’re talking about young people undergoing a huge change from someone who comes in at three pounds of weight, at the smallest end, and eventually grows to be 150 pounds in weight. On top of this huge dynamic range of size, then there’s development. Bone development changes over those years. Just puberty itself creates all sorts of issues related to hormone levels, for instance.

It’s also complex because it depends how you break samples and data down into small groups, by age and ethnicity, for example. For organ-specific conditions there are biomarkers that are grossly abnormal sometimes, but what we don’t know is what is quite normal.

Then we also need collaboration with clinicians, both in defining normal ranges and in regular clinical practice. We can generate a number in the lab, and people don’t always appreciate that this number’s interpretation might differ depending on the clinical situation. Part of the job is to help people interpret the numbers. If you have a sodium level of 140, is a level of 142 really different? Chances are, it’s probably not. Not everybody appreciates that there’s a range, within which variation really doesn’t have clinical significance. My job is to train people to understand that, and to interpret that for people who have questions.