It seems like an easy question to answer: Should the manufacturers of infant formula be allowed to add a new ingredient, found naturally in mother's milk, that many scientists believe may improve the vision of infants and could help children think better as they grow?
The ingredient, which is recommended for babies by the World Health Organization (WHO) and the Commission of the European Community, is available in infant formula throughout Europe and Asia.
But it is banned in the United States, and the Food and Drug Administration has before it an expert panel recommendation to continue that ban for up to five more years.
As the FDA weighs that recommendation, a pitched battle is raging between advocates and opponents of the ingredient, a long-chain fatty acid called docosahexaenoic acid (DHA) that all agree is essential to the development of an infant's brain.
Their highly polarized dispute -- which includes charges of conflict of interest and of sloppy science -- offers an unusual window into the forces that can shape an important scientific and public health debate. The stakes are high: whether the millions of formula-fed American infants are getting the best nutrition possible.
"There is a virtual consensus of specialists in this field that [DHA] should be added to infant formula, and that it will make formula more like mother's milk," said Norman Salem, a senior scientist with the National Institutes of Health.
But the FDA advisers say that neither the safety nor usefulness of adding synthetically produced DHA has been conclusively established, and they urge extreme caution until final results are in. Panel members also accuse the pro-supplementation advocates of mounting an inappropriate political campaign by doctors to sway its recommendation, an effort that dumped more than 1,000 letters supporting DHA supplementation on the panel.
Advocates charge that the panel convened to review infant formula ingredients for the FDA was unfairly weighted against their point of view, and that the financial concerns of a major formula maker appeared to be playing a role in that process. Formula-fed infants, they say, will get less-than-optimal nutrition as a result.
Ross Products of Columbus, Ohio, an infant formula maker long opposed to supplementing with DHA, claims a fast-growing body of scientific research supports its position. Ross officials also point out that supplementing with DHA would be expensive.
"The jury is pretty close to [a verdict] regarding full-term formula," said William McLean, vice president for pediatric nutrition research at Ross, maker of Similac. "The scientific evidence is highly on the side of not adding."
In the middle of the dispute is University of British Columbia researcher Sheila Innis, who was the main fatty acid expert selected for the formula panel. She has long urged great caution about adding DHA to formula, and she also has done considerable work with Ross. Critics charge the panel could not be fair and balanced with her as its primary fatty acid expert.
Innis said that she has been objective throughout and that the panel's recommendation last fall was based on the scientific research available. While acknowledging that she has worked with Ross, Innis said she has worked with other infant formula companies, too.
Proponents of DHA "may well see me as a barrier," Innis said, but she was "walking a difficult line and just trying not to make a mistake by moving too quickly."
After three years on the formula panel, Innis has her own critique of the American process of regulating infant formula. "The different sides have not really sat down to discuss the big picture here," she said. "It's been like having two political teams just going at each other."
The human brain, which many believe is the most complex organ in nature, is made up overwhelmingly of two substances: water and fats. Scientists estimate that between 50 percent and 60 percent of the brain's dry weight is fats, and DHA is one of the most abundant of those fats.
Scientists began to seriously explore the role and importance of these fatty acids in the 1980s. Infants, they found, accumulate DHA in their brains and retinas most rapidly between the third trimester of pregnancy and 18 months after birth, and use the DHA to build the outer membrane of nerve cells during those crucial first months of life.
Because the infant's body cannot convert other fatty acids into DHA very effectively, many scientists believe infants need DHA delivered from outside sources -- from mother's milk or formula. While scientists found that mother's milk does provide high quantities of DHA and other fatty acids, they found that infant formula delivered no pre-formed DHA.
In addition, by the early 1990s some researchers were reporting that babies fed formula with added DHA tended to do better on tests measuring vision and brain function than those fed formula without added DHA. The WHO recommended supplementing with DHA in 1994, in a report that concluded DHA and a related fatty acid should be added to infant formula "in similar proportions to breast milk from well-nourished mothers." Many countries responded and infant and premature-infant formula supplemented with DHA from sources such as fish oils, egg yolks and single-cell algae is available in more than 60 countries.
Some of the DHA-supplemented formula is actually manufacturered by American formula companies in the United States, but none of it can be sold here. That's because the FDA has turned down requests by American formula makers to add DHA, citing inconclusive evidence on its safety and usefulness.
FDA officials said their reluctance to approve DHA has been based exclusively on science. They point to potentially troublesome increases in the weight of the livers and spleens of rats fed very high doses of DHA. They also point to concerns about the physical growth of infants given DHA in some trials a decade ago.
"The FDA has been asked to accept a manufacturer's conclusion that DHA and [the related fatty acid] are generally recognized as safe, and so should be allowed in formula," said George Pauli, of the FDA's Office of Pre-Market Approval. "Our position is this: We don't think there's enough information yet to make that statement. The burden of proof here is on the manufacturer to show it is safe, rather than on the FDA to show it is unsafe."
But advocates say new ingredients are added to infant formula all the time with a fraction of the evidence on safety or usefulness produced for DHA and that DHA-supplemented formula has been on the market for several years in other countries without any known adverse effects.
"Based on what we know about an infant's need for DHA, I think we can say infant formula without it is a deficient product," said David Kyle, a scientist and senior vice president of Martek Biosciences Corp. of Columbia, which produces DHA. Kyle has a vested interest in the subject, but other scientists without those interests share his frustration.
"Every time an issue of safety or efficacy is successfully addressed, another one seems to quickly pop up," said Salem of the NIH.
What, then, makes DHA so controversial? Many of its advocates believe that cost and corporate profits are a key, unspoken factor. Unlike other ingredients added to formula in recent years, DHA would be expensive -- up to 10 cents more per serving.
While infant formula has long been a highly profitable product, changes over the past decade in the federal government's Women, Infants and Children (WIC) program have clearly hurt the formula makers and made them more cost-conscious. The calls to supplement formula with DHA came as those changes were taking place.
A 1989 law required competitive bidding for each state's formula contract with WIC, which buys more than half of all formula sold in the country. The result was dramatic: Within several years, the formula companies were paying huge rebates -- now up to 75 percent of wholesale cost -- to the states. This year, the Department of Agriculture estimates the WIC program will cover about half of all American infants, but will pay only $500 million for infant formula, a saving of $1.4 billion from wholesale cost.
As officials at Ross see it, DHA supplementation will be an all-or-nothing proposition for American formula makers. Overseas, it is available as a premium product. But in the United States, officials say, it would be politically difficult, if not unethical, to deny it to poor WIC infants if DHA was deemed to be valuable.
The FDA announced in 1996 that it would examine the safety and effectiveness of DHA as part of a review of many ingredients in infant formula. The review would be done under contract with the private, nonprofit Life Sciences Research Office (LSRO), which set up the formula panel.
When the panel held a public hearing in spring 1996, the focus was on DHA. Two of the three major U.S. formula makers said that DHA should be allowed, though not mandated. But the third, Ross, was strongly opposed, with vice president McLean at one point ridiculing the DHA advocates and saying of their research, "This is not rigorous science."
Well before the public hearing, scientists had raised alarms over the presence of Innis on the panel. A number of scientists, including Salem of the NIH, told the FDA they did not believe the panel could be objective with only one expert from the fatty acid field who had such strong views.
Another, Thomas Clandinin of the University of Alberta in Canada, an early pioneer in fatty acid research and Innis's dissertation professor in graduate school, wrote the FDA charging that the seven-member panel was not "expert" or "balanced" in the area of fatty acids. "If you put someone on the committee that is working with the segment of the industry that is absolutely against adding these fatty acids to their product, you can pretty much predict the result," Clandinin said recently.
It is not uncommon for scientists to seek and win corporate support for their research, and that private support does not necessarily mean trial results are any less credible. But Clandinin and others felt strongly that in this case, Innis was too closely associated with a company that had a major interest in the issue. The company had supported her lab with some grants and formula, and she had worked with Ross scientists on several studies as well.
Daniel Raiten, a senior staff scientist at the LSRO, said he was offended by suggestions the panel was not objective. Efforts were made to ensure that the panel was balanced, he said, and all members were required to disclose potential conflicts of interest. Raiten also suggested that bias does not only come from relations to industry. Researchers, he said, can be biased by their embrace of a scientific point of view.
FDA officials said they are studying the panel's recommendations -- that DHA not be allowed in formula now, but that the decision be reviewed within five years -- and will take some time before proposing new rules for infant formula. But generally, one senior official said, the agency is guided by the recommendations of expert panels.
Fatty Acids and the Brain
Some makers of baby formula are adding the fatty acid DHA to their products sold abroad in the belief that it aids brain development. Researchers say DHA may benefit:
The formation of myelin, which sheathes nerve fibers and speeds the transmission of nerve impulses.
The branching of nerve cells, which grow and integrate with each new experience.
The synaptic membrane, the portion of the brain cell that makes the connection with another cell.
The synaptic membrane has a higher concentration of the brain-fat DHA than almost any other tissue in the body.
SOURCES: "Smart Fats," "Brain Facts"
CAPTION: Infant formula marketed in Japan contains the food additive DHA, which is recommended by WHO but is banned in formula sold in the United States.