Follow-Up: Genetic Disease Testing and the FDA

In June, I published a post on genetic disease testing after the highly publicized double mastectomy of actress Angelina Jolie, who had the procedure after a genetic screen showed she possessed a version of the BRCA1 gene associated with breast cancer. Consumer genomics has since garnered attention from the US Food and Drug Administration, which claims that manufacturers of home genetics kits are effectively selling unlicensed medical devices. The FDA’s scrutiny of genetic testing recently escalated in a strongly worded letter sent to Anne Wojcicki, the CEO of 23andMe, the largest American manufacturer of these tests.

Anne Wojcicki, CEO of 23andMe, courtesy of 23andMe.

In this warning letter, FDA director of in vitro diagnostics and radiological health Alberto Gutierrez ordered 23andMe to “immediately discontinue marketing the PGS [Personal Genome Service, the company’s genetic testing kit] until such time as it receives FDA marketing authorization for the device.” Although the company has previously attempted to register some of the tests included in the PGS under 510(k) applications, which bypass costly clinical trials by proving that a test is substantially the same as one already on the market, the FDA claims that these efforts are insufficient for the long list of conditions assayed by the kit

The letter focuses on the risks of false positives and negatives, using the same BRCA test that Jolie took as an example. “[I]f the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist.”

Wojcicki has apologized for her company’s failures to comply with the FDA’s past information requests, saying that “We stand behind the data that we return to customers—but we recognize that the FDA needs to be convinced of the quality of our data as well.” However, the company has issued no comment on whether it will discontinue sales of its kits while it prepares regulatory submissions to the government.

UPDATE: 23andMe has announced that while it will continue to sell its kits, it will restrict the results of the tests it releases to its customers to ancestry and raw data. None of the company’s previous health-related claims will be included.


News Flash – FDA to Ban Artificial Trans Fats

WASHINGTON – The U.S. Food and Drug Administration announced Thursday that it had made a preliminary decision to classify the main source of dietary trans fats, partially hydrogenated oils (PHOs), as not “generally recognized as safe” for food use. The public may comment on the decision for a period of 60 days, after which the FDA will choose whether to finalize the action. Should the determination pass, PHOs will be classified as “food additives,” requiring special regulation for continued use.

Donuts containing trans fat, courtesy of BusinessWeek.

A mounting body of research has indicated that trans fats are responsible for a number of deleterious health effects. Their most well-documented impacts are on heart health: trans fats lower “good” high-density lipoprotein (HDL), raise “bad” low-density lipoprotein (LDL) cholesterol, and increase levels of inflammation. Some animal studies have also suggested that trans fat intake could increase insulin resistance, a condition that often leads to Type II diabetes. In light of these risks, New York City passed a widely publicized ban on trans fats in restaurants in 2006, which has been credited with encouraging the FDA to propose the ban at the federal level.

The process for making PHOs was first discovered by German chemist Wilhelm Normann in 1902. By forcing hydrogen gas through vegetable oil on a nickel catalyst, Normann was able to add hydrogen atoms to the molecular backbone of the oil’s fatty acid molecules. The process “straightened” the molecules, allowing them to stack more easily instead of flowing past each other; at the visible level, this turned the liquid oil into a semisolid spread. Proctor and Gamble found that the new fat had useful properties in cooking and increased the shelf life of products in which it was used, and the company began to market the first PHO as Crisco in 1911.

Although small amounts of trans fats naturally exist in beef and dairy products, produced by bacteria living in the guts of cows, these quantities are insignificant compared to the trans fats found in artificial PHOs. If the FDA ban is successful, scientists estimate that roughly a quarter of a million heart attacks, a fifth of those occurring in the U.S. every year, could be eliminated. Restaurants have already been developing new cooking techniques for foods such as donuts and french fries, and Wal-Mart has given its suppliers until 2015 to eliminate trans fats from their products. Together with the ban, these measures are helping to create a healthier food environment for all Americans.

Secret Ingredient – The Science of MSG

As discussed in last week’s article, some creative scientists are examining the changes in Hawaiian seafood menus over time for useful data about fishery abundance. If researchers were to study another set of menus, those of Chinese restaurants in the United States, they would find a similarly interesting trend: from the early 1970s onward, many menus began to advertise the absence of monosodium glutamate, or MSG, in their cuisine. The U.S. Food and Drug Administration, however, has labeled MSG as a “generally recognized as safe” food ingredient since 1959. A sudden change in public perception led to these changes, but the roots of that perception are surprisingly obscure.

Courtesy of

Courtesy of

Although MSG was only formally discovered in the early 20th century by Japanese chemist Kikunae Ikeda, the compound from which it is derived, glutamic acid, is one of the 20 amino acids necessary for proteins (and therefore life itself). The body recognizes the importance of glutamic acid through the sense of taste in foods like asparagus, tomatoes, cheese and meat. Just as the tongue’s taste buds detect sodium chloride as salty, sucrose as sweet, or quinine as bitter, they register glutamic acid as its own unique taste, designated by Ikeda as “umami,” a Japanese word for “delicious” or “yummy” that is often translated as “savory.” MSG is simply glutamic acid that has been stabilized through the addition of sodium; for comparison, MSG contains one-third the amount of sodium per unit volume as table salt.

Asian cooking traditionally derived umami flavor from ingredients such as seaweed (from which Ikeda first isolated glutamic acid) and dried tuna, but by the 1950s, purified MSG was available to the United States as the seasoning Ac’cent. Restauranteurs and food processors were quick to adopt the ingredient as an inexpensive way to bolster the flavor of their products. No concerns were raised by the substance’s inclusion until 1968, when a Chinese-American doctor named Robert Ho Man Kwok reported feeling a number of ill effects after eating at Chinese restaurants in the United States.

As BuzzFeed’s John Mahoney outlines, Dr. Kwok hypothesized in the New England Journal of Medicine that his symptoms may have been “caused by the monosodium glutamate seasoning used to a great extent for seasoning in Chinese restaurants,” and after the New York Times covered the story, a flurry of experiments were conducted to confirm his suspicions. Many of these studies did report an association between high doses of MSG and symptoms such as headaches and flushing, but they lacked the proper scientific rigor of double-blind design (in which both the experimenter and subject do not know which treatment is being administered) or placebo controls.

Better designed experiments over the following decades failed to confirm the results of earlier research, and a comprehensive review by the Federation of American Societies for Experimental Biology concluded that were was no association between MSG and short- or long-term health issues in humans. Despite this research, a number of groups have continued to advocate about the perceived dangers of the compound, and MSG has been absent from baby food since 1969. Yet as the scientific consensus stands, one should feel no fear in enjoying a plate of egg foo young from a Chinese restaurant, even if the menu is silent about the presence of MSG.