From the Deputy Director for Intramural Research

The NIH Intramural Research Program: Our Research Changes Medical Practice

BY MICHAEL GOTTESMAN, DDIR

Most of the readers of this column are aware of the enormous contributions to human health that the NIH has made by supporting basic biomedical research. For the NIH intramural research program (IRP) these contributions are reflected in numerous Nobel prizes to NIH scientists and trainees, other awards, and citations to articles by our highly visible scientists (https://irp.nih.gov/about-us/honors).

An equally lasting impact of intramural research has been felt in medicine’s “standard of care” (what is supposed to happen when you enter a doctor’s office for a check-up, diagnosis, or treatment).

The NIH IRP, including the Clinical Center and its talented clinically oriented scientists, has exemplified the importance of evidence-based medicine, dentistry, and even veterinary medicine. Almost every aspect of clinical practice has been profoundly affected by research done at the NIH.

Let’s say you walk into the doctor’s office for a check-up. Blood is drawn to screen for a variety of disorders, such as disorders of lipid metabolism that could lead to heart disease, stroke, and kidney disease. The original description of low- and high-density lipoproteins and cholesterol, as well as their association with blood-vessel diseases, was worked out at the NIH by Don Fredrickson (NHLBI) and colleagues.

Next, the doctor does a blood count to determine numbers of red cells, white cells, and platelets; to detect malignant disorders of these cells; and to look for infection or bleeding. This procedure used to be a tedious counting process done with a hemocytometer and a microscope. Now diagnostic labs use a Coulter Counter or similar device. The counter was initially developed by Wallace Coulter, an engineer, to count particles in the paint used to protect the surfaces of U.S. Navy vessels. It occurred to him that the principle could be used to measure particles (cells) in blood. The NIH quickly picked up on this concept and developed it for clinical use.

Your doctor is likely to check that your vaccinations are up to date. If you were born in the past 20 years, you would have received in childhood an Haemophilus influenzae vaccine (developed by NICHD scientists Rachel Schneerson and John Robbins to prevent H. influenzae meningitis) and other vaccines—including one for hepatitis A—developed from NIH work. As an adolescent, you would have been vaccinated against human papillomavirus to prevent cervical cancer (NCI’s John Schiller and Doug Lowy developed that vaccine). Later in life, you will receive a high-dose Herpes zoster vaccination to prevent shingles, thanks to the work of Steve Straus, Phil Brunell, and others in NIAID.

Chest pain is a common complaint. If the pain is severe and acute, your doctor will tell you to take a nitroglycerin tablet (and aspirin) and get to an emergency room, as per a protocol developed at the NIH to reduce the damage from occluded coronary vessels. NHLBI’s Andrew Arai, in collaboration with Suburban Hospital (Bethesda, Md.), is working on a quick way to use functional magnetic resonance imaging (fMRI) to determine whether there is restricted blood supply to the heart during chest pain. We expect that use of coronary MRI in emergency rooms will eventually provide definitive diagnostic information in minutes instead of hours. Incidentally, much of the software for interpreting both heart and brain MRIs was developed by NHLBI scientists.

The doctor might discover that a contributing cause of your chest pain is a severe anemia requiring a blood transfusion to improve oxygen delivery to your heart and other vital organs. Rest assured that the blood you receive will not be contaminated with hepatitis virus, thanks to the pioneering work of the Clinical Center’s Harvey Alter, or human immunodeficiency virus (HIV), thanks to Robert Gallo (NCI) who helped develop the first blood test for HIV. If your anemia is due to bone-marrow failure (aplastic anemia), the standard treatment with immunosuppressive agents is thanks to the work of Neal Young (NHLBI).

The future of medicine will include a large dose of genomic analysis. Need I point out that the genetic code was deciphered by Marshall Nirenberg (NHLBI) and NIH colleagues; that the Basic Local Alignment Search Tool (BLAST) algorithm that we use to find related DNA sequences in existing databases was worked out by Stephen Altschul and David Lipman (NCBI, NLM); that many of the genes associated with human genetic diseases were first identified at the NIH and continue to be, through William Gahl’s (NHGRI) Undiagnosed Diseases Program and other studies of rare diseases; and that use of genomic analysis of bacterial genomes, introduced by Julie Segre (NHGRI), Tara Palmore (CC), and Evan Snitkin (NHGRI), will revolutionize the study of epidemics of multidrug-resistant pathogens.

There are hundreds of rare human diseases whose study has been advanced at the NIH; important improvements have been made in treating severe psychiatric disorders such as bipolar illness (yes, lithium was first used for this purpose at NIH, and Carlos Zarate in NIMH has introduced ketamine for rapid treatment of depression); fluoride, shown to prevent tooth decay, was first tested by NIDCR; the use of artificial, surgically implanted mitral valves to replace defective heart valves was an NHLBI first; and the development of single- and multiagent chemotherapy to treat cancer was pioneered at the NCI.

And given that the NIH IRP is one of the most credible sources of medical research in the world, it’s not surprising that many treatments once thought to be effective failed NIH’s rigorous clinical studies (for example, NIDDK tested pancreatic islet-cell transplantation for diabetes; NCI evaluated bone-marrow transplantation after high-dose chemotherapy for breast cancer). I am sure that there are many other examples of how the NIH IRP has influenced health care throughout the world, saving lives and preventing squandering of valuable resources.

At a time when everything that the government does is under increased scrutiny, the NIH IRP seems like a particularly good investment of funds and people.

Sending me any additional examples you have of how the IRP has improved medical care would be much appreciated.