From the Desk of Dr. Louis M. Weiner

On Saturday, our nephew Brandon came down for the day to visit us and see the Georgetown-Villanova basketball game. Like Harriet and me, Brandon is a Philadelphian. He is a recent college graduate, and is trying to make a go of it in the area of video productions. Being a sports nut, he of course wore his Villanova basketball jersey to the game. The game attracted the largest crowd of the season to the Verizon Center, though it was not much of a contest — Georgetown won quite easily. It was easy for me to root for Georgetown against this particular Philly team. When when I went to Penn, Villanova was a bitter basketball rival. We had a great timeat the game, and found a nice little Chinese restaurant near the Verizon Center as a bonus.

What struck me about the game was how central the basketball program is to the culture of Georgetown University. I know this is not terribly unusual;Penn State has always been shaped around its football team, and who can think of Duke University without considering its basketball team? But I actually think a basketball home game is the best place to “run into” a colleague for a brief business meeting! And, it is certainly a wonderful way to truly understand this university — its fundamental civility, wit and genuine exuberance.

If Brandon had worn a Georgetown University uniform to a Villanova-Georgetown game in Philly, he would have left drenched in beer, at the very least. But at the Verizon Center the Georgetown student rooting section merely began to point at him, shouting “Put it on!”, referring to the free Georgetown tee shirt at each seat in the arena. Another Villanova fan actually was offered a beer (no, not on his head) by one of the students who had heckled him in a good natured way.

It was a nice moment, and it was good to think that this is one place where sports are important but genuinely placed in a proper perspective. And it is always thrilling to know that the phrase “Georgetown Basketball” defines a broader civic virtue that is embraced by the larger metropolitan area of Washington.

Let’s continue working so that one day soon the phrase “Georgetown Lombardi” will occupy a similar niche in the heart of Georgetown University and in the consciousness of this city. What we do matters — and we don’t need the offer of a beer to know that.

On Friday I received a message I had been dreading. My friend and colleague, Lou Houston, had died, peacefully and surrounded by his family at his home near Seattle.

Lou was about 70, and had battled his cancer, a mucinous adenocarcinoma of the peritoneal cavity, for nearly a decade. He had undergone several aggressive surgeries, with various forms of intraperitoneal chemotherapy, and had also received several different forms of systemic chemotherapy during the course of his illness. At the end, he was on total parenteral nutrition (iv feeding) because his gut no longer worked. His type of cancer is fairly unusual; when oncologists counsel patients with this disease, we may reassure them that this is one of the “good” cancers to get, as patients tend to do well and may survive for years. Tell that to Lou’s family now…

This unusual malignancy has no identified molecular signature and as a result, it is hard to do anything that is not basically empiric in nature. And, because of its relative rarity, it is hard to obtain solid evidence from randomized clinical trials to guide the choice of empiric therapies. Finally, because it is rare and molecularly mysterious, it’s hard to know how to assess risk for the development of the cancer, or how to prevent it. This perplexing set of factors characterizes many of the cancers we see and treat; clearly the answer lies in the systematic implementation of molecular analysis to uncover the causes and potential targets for all cancers.

Ironically, Lou would agree with me wholeheartedly. He was a biochemist who had trained at the University of Kansas (and knew everything worth knowing about their basketball team). I first met him a little more than 20 years ago. Those of you who read last week’s blog may recall that I recently saw Ed Bradley, whom I first met when I collaborated with Cetus Corporation to develop a bispecific antibody. Well, Ed connected me with Lou, who was pioneering recombinant immunotoxins that used an antibody fragment to deliver recombinant ricin A chain to breast cancers at Cetus. Lou was organizing a group of collaborators to develop this concept with the support of a National Cooperative Drug Discovery Group (NCDDG) grant. I got involved, we got the grant, and I began a series of collaborations with Lou, and with other outstanding scientists such as Jim Huston (who initially described single-chain Fv antibodies) and Jim Marks (who worked with Greg Winter to develop antibody phage display, and affinity maturation techniques), among others.

Lou was the consummate leader, scientist and friend. He was open, interested, generous and incredibly insightful. The NCDDG created novel molecules, spawned the careers of numerous investigators, and certainly made major contributions to the field of antibody engineering. Lou eventually moved on to other scientific ventures, always looking for cancer-related molecular signatures, and for ways to develop novel therapeutics directed against important targets.

I should add that he was a marvelous host; I had several meals at his home, graciously presided over by Lou, his wife Terri and by a fabulous piece of salmon courtesy of his son Scott, who is a Seattle-based salmon broker. Over the past five years or so, his energy and focus had necessarily waned as he fought his illness, but until recently he was always looking for the next big opportunity to make a difference.

Nearly 500,000 Americans will die of cancer this year. Not everyone will have had the impact that Lou had in his life, but each of them will have his or her own unique and important story. The same is true of the cancers that took their lives. I am glad that we have the privilege and opportunity to do something to change the plots.

For those of you who read my blog last week about my young patient with newly diagnosed metastatic colon cancer, I intend to provide occasional updates.He had an infusion port placed last week, and started receiving chemotherapy. I spoke with his surgeon in some depth, and we plan to start with chemotherapy and then hope we can remove the primary cancer and the liver metastases at a future date. So far, so good.

But in one major way we are flying blind — without useful knowledge about his particular tumor’s biology that can help us truly customize his therapy and give him the best possible chance for effective therapy and cure. So, 40 years into the molecular biology revolution, we still rely upon empiricism and “clinical judgment”rather than on actionable knowledge that can drive innovation and improvetreatment outcomes. Now you know why I rant about the importance of personalized medicine as the basis for future advances.

Last Monday, I joined John Marshall and Ruth He at a dinner meeting with representatives from Medimmune to discuss possible clinical trial collaborations. One of the Medimmune representatives was Ed Bradley. I first met Ed about 25 years ago, when I was a young faculty member. I wasdoing laboratory and clinical research with monoclonal antibodiesdeveloped by Cetus Corporation, where Ed worked at the time. A delegation from Cetus visited Fox Chase Cancer Center, and at a meeting with them I was offered the chance to clinically develop either a conventional antibody or a new type of “bispecific” antibody that had never been tested in a clinical setting.

The former choice was safe and certain to lead to aclinical trial, but I had begun working with bispecifics in the lab andhad just submitted my first R01 (which got funded) to study bispecifics.So, although bispecific antibodies represented a high-risk, high-reward opportunity, I took a deep breath, selected the bispecific and in doing so, set the stage for my career as a laboratory scientist and clinical investigator. That experience taught me that good science involves risk taking, and since then I have never been afraid of new challenges, new concepts or new technologies. So, for those of you who know your Proust,seeing Ed was like biting into a Madeleine, and then being flooded by memories. It was a nice moment.

Continuing with that theme, I spent Thursday at Fox Chase Cancer Center, as a new member of Fox Chase’s External Advisory Board. I had been away for four years, so walking through the halls was a bit disorienting– both warmly familiar, but not quite the same. I saw many old friends, but I passed many other people in the halls without a flicker of recognition by me or by them–time moves on, and people come and go.

I wasn’t sure how I would feel, but I embraced the opportunity to provide assistance to so many good friends and former colleagues, and on balance finished the day feeling good about my decision to serve on their EAB. I then scurried backto DC so I could  host Erica Golemis’ terrific talk as a Visiting Professor; Erica is a friend and collaborator who is based at Fox Chase.All in all, I felt as if I had taken another bite of the Madeleine.

We are all formed by the summation of our experiences, and I am genuinely grateful for all of the wonderful people I have had the privilege of working with over the years. I am doubly excited to know that every day, in countless ways both large and small, I am accumulating  experiences and treasured  memories at Georgetown that will no doubt be a feast of Madeleines for many years to come.

So, I write this blog after the Super Bowl. It was an exciting game, but I must confess to being very suspicious about a team that somehow was able to lose to the Redskins twice during the regular season. Talk about parity … I can’t say I was crazy about the commercials or the halftime show.

Delaying the blog gave me a chance to think about what really affected me most last week — a new patient I saw on Thursday. He is a 31-year-old man,married, with a wife, a small child and another one on the way. Almost unimaginably, he has newly diagnosed metastatic colon cancer, and no family history or antecedent medical problem that suggests he has a known genetic predisposition. There is a small chance that he can be cured with an aggressive blend of chemotherapy and surgery, but this is a very tough situation.

It’s funny how some patients manage to penetrate the semipermeable membrane that protects oncologists from the personal tragedies we witness on a regular basis; I guess he has done so because he is only three weeks older than our oldest son, and I know how exciting it is to be approaching the true fullness of one’s adult life, with a seemingly limitless time horizon stretching ahead. And then, the impossible happens.

If anything can remind me that what we I do as a doctor is important, this young man’s illness will serve. And, if anything can remind me that what we all do — striving to understand, prevent, treat and cure all types of cancer — is very important, this little vignette will do too.

Time to go back to work.