Downstate Medical School Graduation

May 24, 2005
at Carnegie Hall

Thirty-nine years ago, I was supposed to be receiving my medical degree from another institution in this city in front of my proud parents. Instead, I was indulging my wanderlust in the mountains of Kashmir. So I know from my own negligent behavior how important it is for the graduates who are here today to give homage to the families that helped you to come as far as you have.

I do remember feeling something on my graduation day in the mountains of Kashmir that most of you now feel -- a sense of accomplishment of having learned an enormous amount about human biology and disease and knowing what I would need to know to take care of patients as an informed member of a hospital staff.

I may have been right about the accomplishment, but I was wrong about the sufficiency of my knowledge. Maybe I had learned (and you have now learned) the facts essential to practice medicine on graduation day. But let me assure you, the learning has just begun. This is so, not because you haven't learned much of what is known. It is so because science and medicine are now evolving at such a great rate.

It is especially easy to see this by looking back over the years since I was awarded my degree in 1966. There was so much I didn't know simply because it was not yet known.

For example:

• Neither I nor my father, also a physician, could have known or even predicted the importance of diet, exercise, lipid-lowering drugs (statins), angioplasty, anti-coagulants, vascular surgery, or even an aspirin a day for drastically reducing the incidence and mortality of the heart disease that killed him a few years after my graduation.
• No one could have told me in 1966 about the variety of infectious diseases that were soon to appear on the international scene, including SARS, hantavirus infections, Legionnaire's disease, Lassa fever, and, most obviously AIDS. HIV had not been isolated; the concept of a retrovirus was only in the mind of a single neglected scientist. The notion that we could effectively treat a lethal viral infection with a cocktail of enzyme-inhibiting drugs was beyond comprehension.
• The understanding of the chemical underpinnings of mental disorders was primitive, and our current repertoire of effective antipsychotic and antidepressive drugs was unimaginable.
• No one knew anything about embryonic stem cells, the methods for growing them, and their potential for treating a multitude of human ailments.
• No one had isolated a gene, let alone determined the sequence of its nucleotides. We didn't know anything about the recombinant DNA methods that gave birth to the biotech industry and have now delivered human insulin, growth hormone, and effective antibodies against cancer cells. The concept of gene therapy was purely science fiction.
• We could not have imagined another product of the biotech industry, the vaccines that can prevent the common cancers associated with hepatitis B or papillomavirus infections, in part because we knew so little about these viruses and had not recognized them as causative agents of hepatoma and cervical cancer.

I could continue with this list, but we have only a few minutes together. Instead, let me tell you a short story that illustrates how quickly medicine is changing in response to some recent science.

Until a few years ago, doctors had little to offer patients with lung cancer unless the tumor was found early enough to be removed surgically. And still about 90 percent of the 170,000 new lung cancer patients in the US each year eventually die of their disease.

On February, 2, 2002, a young woman with disseminated lung cancer entered our outpatient department in a wheelchair, breathing from an oxygen tank. She had exhausted all conventional chemotherapies and chose to enter a trial of an experimental drug. This drug was tailored to inhibit an enzymatic activity, a so-called tyrosine kinase, an enzyme that is part of the receptor for the epidermal growth factor called the EGF receptor. Within just five days, she was out of her wheelchair, breathing normally and feeling good, and her chest x-ray was nearly normal. What was happening? And why to this patient and a few others, but not for all patients with lung cancer?

The scattering of patients around the country who were having such miraculous responses to the enzyme inhibitors attracted a lot of interest in our lab and others. In less than two years, using methods to analyze tumor DNA, it was discovered that the cancers that responded to these drugs contained mutant receptors in the place of normal EGF receptors. The drugs were killing cancer cells that carried unusual mutations in the EGF receptor gene.

This was exciting but still didn't have long-term benefits for the patients. Most of them developed resistance to the enzyme-inhibiting drugs in less than a year. Indeed our own patient relapsed and died about 14 months after her remarkable remission.

But it didn't take long to find out why the tumors become drug-resistant. Within eight months, we knew that at least half of them acquire a second mutation in the EGF receptor gene, blocking the inhibitory action of the drugs. And now, just a couple of months later, it has been possible to identify other drugs that can inhibit even the doubly mutant receptor.

Obviously this pace of discovery is dizzying to physicians and scientists. Moreever, it gives real hope for the patients with this type of lung cancer. It also encourages the belief that all lung cancers -- not just the ten percent with EGF receptor mutations -- and indeed all cancers, will eventually be treated with drugs and antibodies that counter the specific genetic damage that gave rise to the cancers in the first place.

These developments with lung cancer, a common and lethal disease, are probably news to most of you -- and perhaps to many of your teachers -- because they have just occurred during the past year.

So how will you learn about these exciting new things in the future, especially when you have lost your connections to the SUNY library system and no longer have your teachers to guide you?

Fortunately, a new movement in medical publishing is coming to your aid---one that is based on providing full and immediate access to the scientific and medical literature through a public digital library, so that you can easily search for the right information and get it, freely and immediately, when you need it.

This open access movement --in which I have played an active role, and have the bruises from certain for-profit publishers to prove it -- has been built on the potential for transmitting, storing, searching, and sharing information on the Internet. Open access publishing also builds on the idea that publishing is part of the cost of doing research, that funders of research should pay publication costs. In this way, the articles can be provided to all for free. The public (which pays for most of the research in the US through taxes) can have access to it, and scientists and healthcare personnel can use it optimally.

Your support for this exciting development in publishing will help bring it to fruition, will help you to keep up with the rapid advances in medicine, and will bring the benefits of medical science to your patients more quickly. In this way, you will be able to adapt more easily to those many changes in medicine that will occur over the next half century, even though you cannot anticipate them now. And you will be fulfilling the highest ideals of the medical profession.

Good luck to all of you! And congratulations!