Proving 'Ingredient Safety' is a challenge - Who do you trust?

Director Michael Holsapple discusses the controversy surrounding the "Impossible Burger".

August 21, 2017 - Michael Holsapple

Michael Holsapple is Director of the Michigan State University (MSU) Center for Research on Ingredient Safety (CRIS) and Professor in the Department of Food Science and Human Nutrition.  He is also a toxicologist with over 35 years of experience.

I was encouraged to consider the controversy associated with a genetically-engineered (GE), plant-based burger patty.  The controversy over the “Impossible Burger” is not new; but the debate was recently intensified because of an article published in the New York Times on August 8th – Impossible Burger’s ‘Secret Sauce’ Highlights Challenges of Food Tech.  I decided to focus my attention on one of the founding principles behind the creation of CRIS – e.g., that consumers should be encouraged to make evidence-informed decisions.

I wasn’t sure exactly where to begin to consider the evidence, so I visited the website of Impossible Foods.  The following statement on their homepage, caught my eye,

Trying new things can be risky.  Not trying new things & staying on our current trajectory is even more risky.”

If one were to extend this statement to the question at hand, one would have a statement that could look something like,

“Trying the ‘impossible burger’ can be risky.  Not trying the ‘impossible burger’ and staying on our current trajectory (e.g., eating beef burgers?) is even more risky.”

Neither of these statements are particularly helpful to a consumer trying to understand the basis for the concern expressed in the NY Times article – Is the “Impossible Burger” safe?  Or, perhaps more appropriately, is the “Secret Sauce” – as captured in the title of the NY Times article, and described in the body of the article – “soy leghemoglobin, a substance found in nature in the roots of soybean plants that the company makes in its laboratory” – safe?

A number of important questions were raised in the NY Times article including the general debate over the safety of GE products.  If you visit the CRIS website, you will find my position on the GMO / GE debate – Are GMOs Bad?  Experts Pick Sides.  I also participated in the Forum of Scientific Society Leaders on GE Crops.  This link provides access to some of the comments that I made during that Forum, which was convened to consider the report from the National Academies of Science, Genetically Engineered Crops:  Experience and Prospects.  I also played a leading role in developing a commentary subsequent to that Forum, “National Academy Report on GE Crops Has Support of Scientists from Wide-Ranging Disciplines”, which was published in Nature Biotechnology (Vol. 35; No. 4; Pgs 304 – 306, 2017).  Our commentary ends with the following – “Overall, the NAS report provides an updated and authoritative summary of scientific evidence related to the agronomic, health, environmental, and socioeconomic effects of GE crops. The report addresses many criticisms of GE crops, but appropriately notes that the field is rapidly changing. Future GE crop traits are likely to offer opportunities and risks that are different from the current mix. As a result, rather than succumbing to ‘political correctness’, the NAS report refrains from blanket statements that all GE crops are inherently risky or safe. Rather, the report describes that GE technology per se raises few risks not inherent to other modes of crop improvement. Accordingly, the report points to the need for public dialog and regulatory review processes to pay more attention to the genetic traits resulting from new technologies, rather than the processes by which traits are created.

The ‘bottom line’ is I don’t believe that, just because something is produced via genetic engineering, it is inherently un-safe!

Another one of the important questions raised in the NY Times article addressed the potential problems associated with the process known as GRAS (e.g., Generally Recognized As Safe).  Specifically, the article makes the following comments – “The FDA’s approval is not required for most new ingredients.  Companies can hire consultants to run tests, and have no obligation to inform the agency of their findings, a process known as ‘self affirmation’”.  I looked for the specific evidence, and determined that, in August, 2014, Impossible Foods did engage some well-respected experts in toxicology, allergenicity, and food science (e.g, microbiology) who conducted a full literature search to identify any published literature regarding possible toxicity or allergenicity associated with hemoglobin proteins, and to identify any reports regarding health issues associated with human consumption of hemoglobulin proteins of any origin.  The expert panel offered the following conclusion, “We unanimously conclude that the proposed uses as a protein component in meat and poultry replacement (analogue) products of soy leghemoglobin, produced consistent with current Good Manufacturing Practice (cGMP) and meeting the food grade specifications presented above, are Generally Recognized As Safe (GRAS) based on scientific procedures (structural and functional equivalency to other safe plant and animal hemoglobins).

There are two other factors with the GRAS determination of soy leghemoglobin that are worthy of mention.  First, there is considerable focus on improving the transparency of the GRAS process, as conveyed in the document from October, 2016 – Frequently Asked Questions about GRAS for Substances Intended for Use in Human or Animal Food:  Guidance for Industry.  There are a couple of points made in this document, that are particularly relevant to a discussion about the conclusion that soy leghemoglobin is GRAS.

How are the criteria for eligibility for classification as GRAS similar to the criteria for FDA’s approval of a food additive? Regardless of whether the use of a substance is a food additive use or is GRAS, there must be evidence that the substance is safe under the conditions of its intended use. FDA has defined "safe" as a reasonable certainty in the minds of competent scientists that the substance is not harmful under the conditions of its intended use. The specific data and information that demonstrate safety depend on the characteristics of the substance, the estimated dietary exposure, the population that will consume the substance, and other relevant considerations.

How are the criteria for eligibility for classification as GRAS through scientific procedures different from the criteria for FDA’s approval of a food additive? The difference between the criteria for eligibility for classification as GRAS through scientific procedures and FDA’s approval of a food additive relates to who has access to the data and information and who has reviewed those data and information. For a substance to be GRAS under the conditions of its intended use, the data and information relied on to establish the safety of the use of the substance must be generally available (e.g., through publication in the scientific literature) and there must be a basis for a person to conclude that the substance is generally recognized, among qualified experts, to be safe under the conditions of its intended use. In contrast, for FDA’s approval of a food additive privately held data and information about the substance under the conditions of its intended use are sent by the sponsor to FDA and FDA reviews those data and information to determine whether they demonstrate that the substance is safe under the conditions of its intended use.

The second factor associated with the GRAS determination of soy leghemoglobin was also briefly mentioned in the NY Times article, “Impossible Foods adhered to that procedure (e.g., GRAS determination via self-affirmation), concluding in 2014 that soy leghemoglobin was safe.  But it went further, seeking the regulator’s imprimatur.”  They are quoted in the NY Times article, “We respect the role the FDA plays in ensuring the safety of our food supply, and we believe that the public wants and deserves transparency and access to any information they need to decide for themselves whether any food they might eat is safe and wholesome.”  The latter statement is amazingly aligned with one of the overall goals for CRIS – e.g., to facilitate the ability of consumers to make evidence-informed decisions.  So, I tip my hat to Impossible Foods for their stated commitment to transparency.  However, the FDA responded to the GRAS declaration for soy leghemoglobin by emphasizing that this request was based on a history of safe use of soy proteins, and did not specifically discuss the fact that soy leghemoglobin, as derived from the roots of the soybean plant, was not a commonly consumed human food, and as such, could not be Generally Regarded As Safe.

But that is not the end of this story, as the CEO of Impossible Foods released An Open Letter from our CEO on August 10th.  This letter conveys many of the same points that were either made in the NY Times article, or are highlighted above.  There are a few points that are included in this letter that are worthy of being mentioned here.  First, the CEO of Impossible Foods emphasized that “We wanted the FDA to review our GRAS determination, to have the added benefit of their expertise, and to assure customers that our testing of leg hemoglobin has passed the most rigorous scrutiny.”  Of course, based on what you have learned about the GRAS process, you can easily see that it is far from being “the most rigorous scrutiny”.  The CEO goes on to state that “After submitting our GRAS determination, the FDA reviewed it, and had some questions.  To address them, we conducted additional tests . . . no adverse effects in rats consuming soy leghemoglobin every day for a month at levels more than 200 times what an average American would consume if all the ground beef in their diet were the Impossible Burger, and very low risk of allergenicity”.  While this new study is important, the real analysis will take place when these results are made publicly available, and the scientific community can judge the validity of the study design to determine the ‘safety’ of consuming high levels of soy leghemoglobin, and can come to grips with the statement, “very low risk of allergencity” – e.g., studies in rats are historically difficult to determine whether a component of foods has the potential to be allergenic in humans.  As noted in the letter from the CEO, “Impossible Foods has always worked constructively with the FDA, whose role as guardian of food safety for the nation we deeply respect.  We will be submitting the additional data . . . to the FDA this month.  And FDA will make Impossible Foods’ submission – hundreds of pages of safety and allergenicity test results – publicly available on its web site soon thereafter”.  As noted above, the Guidance for Industry report from 2016 makes the following point, “For a substance to be GRAS under the conditions of its intended use, the data and information relied on to establish the safety of the use of the substance must be generally available (e.g., through publication in the scientific literature)”.  It will be interesting to see if Impossible Foods goes beyond making their results publicly available on a web site, and actually tries to publish the results of their most recent study in the scientific literature. 

I have one final point to make from a decidedly personal perspective – e.g., living with someone who has celiac disease.  It is encouraging to note that the CEO declared in his open letter, “In addition, . . .  we clearly label our product as containing potential allergens:  wheat and soy – also in compliance with federal regulations”.  However, that being said, it is disappointing that he prefaced this declaration by emphasizing “in an abundance of caution”.  Being transparent should not be something that a company does to be cautious – rather it is something that a company should do to enable consumers to make informed choices.

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