The Opposing Thumb

An opinionated digit leafs through the biological literature
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ZEEV PANCER (1957-2014)

zeev

Image by Madalena Parreira.

You are not a real scientist until you make a discovery. And if you make a great discovery, you’re a great scientist– E.O. Wilson.

Once upon a dinner, many years ago, a young OT was seated next to a Grand Old Man of Science. Grand asked Opposing, in a gruff old manner, without prior niceties or formal introductions, “so, what was your most interesting discovery?”  OT tried to get away with some inane wisecrack about gummy bears and microwaves. Had the question been “what was the most interesting discovery you were ever within 50 feet of?”, the answer would have been easy, immediate, and involve no candy or appliances.

Zeev Pancer worked on many problems that orbited the larger issue of the evolution of immunity. In Israel, he had studied the evolution of molecules that orchestrated acute inflammation. In Germany, and later at Caltech, he discovered a large cluster of immune genes in marine invertebrates.

Exactly how he made his way to Dixie in the early 2000s is a mystery. OT first met Zeev in Alabama, going out for a beer with a mutual friend, who promptly warned “don’t ever try to take on Zeev one on one”.  Opposing was being cautioned that Zeev had a ferocious intellect and was very serious about science. Over the next couple of years OT modified this advice, and told others “don’t ask Zeev a question unless you really, really want to know the answer”. He was intense, uncompromising and very intelligent- just the person you wanted scrutinizing your data and ideas. If you could then pick up, separate and piece together the fragments of your hypothesis and your ego, then you’d had an evening that was worth a dozen lab meetings.

The problem Zeev chose to tackle in the Deep South would certainly have made Grand Old Man sit up straight and listen attentively. Jawed vertebrates, the extended family that includes all branches of the tree of life between sharks and us monkeys with iphones, all share a fundamentally similar immune system. We all make lymphocytes, a special class of white blood cells. Lymphocytes are very uninteresting in a blood smear, small and round and all the same. But genetically, they are the most intrepid cells in the body. During their development, all lymphocytes scramble the genes for the molecules they use to recognize foreign (or self) molecules and trigger immune responses. Each antibody is genetically unique, formed (more or less) at random by gene shuffling in the maturing lymphocyte. The basic idea is that this gives us, sharks and monkeys, a chance to keep up with the genetic diversity of bacteria and parasites that can take as little as 30 minutes to reproduce (to say nothing of the fantastic genetic variability of viruses).

All of these genes appear instantly, in evolutionary terms, at the branch point between jawless vertebrates (lampreys and hagfish) and cartilaginous fish (sharks and skates). In 2004, Zeev and his collaborators in Max Cooper’s group at the University of Alabama at Birmingham made a stunning discovery: lampreys (and they later showed the same for hagfish) had evolved in parallel an entirely different hyper-variable immune system. Cells that looked like lymphocytes in the lamprey blood used a completely different set of antibody genes, and a novel genetic way of shuffling them, to achieve the same result: a clonally diverse set of circulating cells that responded specifically to different infectious agents.

Comparative approaches are at the heart of Biology. They allow us to separate historical contingency from universal principles. Zeev and his collaborators gave us not only a fascinating new immune system to study in its own right, but also a mirror we can hold up to our immune system and examine its strengths and weaknesses, to look beyond the superficial at the underlying character. We can ask new questions. Are the rules the same? Do these adaptive immune systems see the same things? Do they learn to tolerate the host tissues in similar ways? Are there autoimmune diseases in jawless fish?

According to the tribute page at the Institute for Marine and Environmental Technology where he worked, Zeev was working on creating a ‘“synthetic immune system” by grafting to yeast the essential components of adaptive immunity.”’ An original, creative, and technically challenging project. A project that might have failed utterly or taught us things no one else’s work would. A Zeev Pancer project.

Zeev died on April 20th, in Baltimore.

 

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