Published June 4, 2018
UB professor of biochemistry and pediatrics was on the team that pioneered newborn screening programs worldwide
Newborn screening programs to detect serious metabolic disorders before they become symptomatic are now well-established in all developed countries and have been introduced to a greater or lesser degree in just about every inhabited region of the earth. And it all began at UB in the 1960s.
Robert Guthrie, MD, PhD (1916-1995) was a research microbiologist at Roswell Park and UB’s medical school when he invented a simple test for phenylketonuria (PKU), a rare inherited disorder that causes severe brain damage unless it can be treated before symptoms appear.
The test begins with a pin prick to the baby’s heel and a drop of blood on filter paper. After it dries, the sample can then be sent to a lab for analysis. Millions of such dried blood samples have been collected on so-called “Guthrie cards” since he invented the technique in 1961.
“By collecting the sample as a dried blood spot on a piece of filter paper rather than liquid blood in a tube, he really came up with something that was simple but brilliant,” said Michael Garrick, PhD, a professor of biochemistry and pediatrics in the Jacobs School of Medicine and Biomedical Sciences Department of Biochemistry. He was recruited to UB by Guthrie in 1970.
Guthrie himself compared it to the invention of the safety pin: something simple and useful that seems obvious, but only in hindsight.
“It was obvious by the time I was hired that you were going to have newborn screening everywhere,” said Garrick. In addition to PKU, Guthrie’s lab was searching for other disorders that could be detected through neonatal screening. “I worked on a number of tests,” said Garrick. “We succeeded in the sickle cell test.”
Having the technology to detect hemoglobin SS (the defective form) wasn’t enough to ensure that it would translate into a workable therapeutic, however. “I knew from Guthrie that we ought to get the parent-physician advocate groups involved in order to gain acceptance,” said Garrick. “That was the model when I got here: you tried to associate with the people who care.”
Guthrie and his wife were active in the Erie County chapter of an organization that was then called the National Association for Retarded Children (NARC). Their son John had been born with a serious cognitive impairment and a niece was diagnosed with PKU too late for help. He became a zealous proponent of newborn screening, and he knew how to sell it.
Some colleagues at Children’s Hospital put Garrick in touch with a physician who could help implement the “Guthrie model” for sickle cell testing. Lydia Wright, MD, was a pediatrician well known in Buffalo’s African American community.
“We hit it off right away,” recalls Garrick. “She was taking a lot of patients where she wasn’t going to get paid. A lot of these patients couldn’t afford to have a sickledex test (the standard sickle cell screen), even though it’s not that expensive.”
So Garrick struck a bargain with Wright. “Anytime she sent us a dried blood spot, we would check it out for sickle cell. And in turn, any time we found someone that we thought might be SS, we would refer them to her. She would introduce herself to the parents, verify the diagnosis, educate them about the disease, and begin treatment.”
In time, Garrick and Wright helped launch the Niagara Frontier Association for Sickle Cell Disease, a patient support and interest group. Wright (1922-2006), the first African American pediatrician in Buffalo and the first to serve on the Buffalo Board of Education, was a tireless community activist. Public School 89 was renamed the Dr. Lydia T. Wright School of Excellence in her honor in 2000.
When the New York State Assembly was holding hearings to determine whether or not to add sickle cell anemia to the list of disorders that all New York newborns would be tested for, Garrick and Guthrie were called to testify. “I argued against my own test,” Garrick said.
Some people had been calling the screen a “bad news test,” since there is no cure. He argued that the state should conduct a controlled experiment to see if early diagnosis actually benefited patients.
Guthrie, on the other hand, had no such qualms. “Guthrie believed that we should just have the government order it and we should do it,” said Garrick. “He went in there and he said, I think black parents care just as much for their kids as whites do, and I’ve seen how much white parents care.” Based on his experience with NARC and PKU, Guthrie was convinced public pressure would force improvements in disease management once universal screening was implemented.
He won. The test was mandated for all New York newborns in 1975. Since that time, approximately 250,000 New York babies have been tested annually for hemoglobin SS, resulting in about 100 to 150 diagnoses a year, according to the New York State Department of Health.
Ironically, Garrick’s test was soon subjected to the controlled experiment he wanted, albeit not under ideal conditions. That was the year President Ford refused to bail out New York City from a severe fiscal crisis. Testing for sickle cell disease was mandated, but follow-up with patients was not.
“After New York City emerged from bankruptcy, they cooperated through Albany to go track down all the kids that they had detected for several years and not done anything about,” said Garrick. “Meanwhile they compared them to all the kids in the rest of the state who had received medical attention following their diagnosis. Not one had died in the rest of the state; 10 percent did in New York City.”
Children with SS are at high risk for pneumonia. With an early diagnosis, they can be treated with pneumovax in time to forestall the complication. Parents who are educated about their children’s disease are better able to cope with other complications, too. Splenic sequestration crisis, another common side effect of sickle cell disease, can require an emergency blood transfusion to save the patient’s life.
“That was the beginning of the improvements,” said Garrick. “Obviously, the more cases you get the better the clinics get at managing these things. They know that the early diagnosis is helpful to them because they don’t need time to figure out in many of these cases what’s causing the problem.”
Nationally, about 1,000 cases of sickle cell disease are diagnosed through newborn screening per year. Given a 10 percent fatality rate for kids left untreated, that means something in the neighborhood of 4,000 lives have been saved thanks to Garrick and Guthrie’s efforts to mandate screening.