Public good vs. real world
There is nothing unusual about medical researchers and corporate executives spending years and many millions of dollars in search of cures or treatments, only to end up at a clinical dead end. It happens all the time.
The history of people and companies chasing the development of human blood substitutes is a whole other story, and what a story they could tell. It's a classic about the public interest running headlong into the real world.
The latest chapter appeared yesterday in the form of a study published in the Journal of the American Medical Association. The study and an accompanying editorial said a broad review of 16 clinical trials for five different products would have shown significantly higher risks of heart attack and death as early as 2000.
The authors say the Food and Drug Administration should have seen the signs and put a stop to blood substitute experiments until safety problems were resolved. FDA officials say they have been on top of those issues from the start and have done the right things in individual cases. No blood substitutes have been approved by US regulators for commercial use.
Many companies have pursued the development of blood substitutes using hemoglobin, the molecule that delivers oxygen in red blood cells. One of those companies, Biopure Inc. of Cambridge, and its product derived from cow blood have been familiar subjects in this space over the years. More on them later.
Human blood substitutes have some clear advantages over the real thing. Many have a relatively long shelf life and can be administered without regard to blood type. Their usefulness in military situations and civilian trauma cases is clear.
Military interest was behind the earliest commercial research into blood substitutes decades ago. But Wall Street really got excited at the dawn of the AIDS era, when real questions were raised as to how the nation's blood supply would be protected. As it turned out, the threat to the blood supply came and went. But some companies were fully engaged in the hunt for a safe and practical substitute. Serious money was raised.
Here's the problem: No one ever really came close to clearing the bar. Even worse, serious medical complications were first recorded a long time ago.
Baxter International Inc., an early entrant in the blood substitute hunt, gave up more than five years ago after spending $500 million. Baxter had to halt a study of its HemAssist product in 1998 when nearly half of patients that received it died, compared with about 17 percent of patients treated with conventional therapy.
At about the same time another company, Northfield Laboratories Inc., was testing its own product, called PolyHeme. The results were not good, especially when it came to higher rates of heart attacks among patients who got the blood substitute, and the trial was quietly stopped.
Then Northfield tried again several years later, testing its blood substitute with or without the consent of trauma patients who were sometimes unconscious. Northfield promised public awareness campaigns about the trials and told people who didn't want to participate to wear blue plastic wristbands to alert paramedics who might find them unconscious and in need of help. I can't make this stuff up.
The real catch: Northfield never publicly fessed up to the original results until The Wall Street Journal published a story about it in 2006. The company said inexperienced doctors may have been to blame.
Finally, there is Biopure, the Cambridge company working with cow blood. I got an earful from the company's former chief executive when I wrote critically about Biopure's efforts in 2001. His company's stock was worth more than $500 million then. It's worth $17 million today.
Biopure tested its Hemopure product on elective surgery patients. No one ever complained the company misled doctors. But the Securities and Exchange Commission eventually decided executives had not been straight with investors about the trials. It neglected to mention some of the FDA's reservations about the product. Another former chief executive of Biopure eventually paid a $120,000 fine to settle fraud allegations.
More recently, Biopure has found a big supporter in the US Navy. It wants to see how Hemopure would perform in a test of 1,000 civilian trauma patients. The FDA said no way. The company's still trying and says the study published yesterday is flawed.
The authors of that study argue that the experience with blood substitutes shows how FDA rules that keep commercial test results confidential can lead to dangerous "secret science" that should not be permitted. Maybe that's a stretch, but you tell me how the public interest was well served by the fake blood experience.
Steven Syre is a Globe columnist. He can be reached at syre@globe.com.
