Gilbert V. Levin, Ph.D.

The Brains Behind the New, Low-Calorie Sugar, D-Tagatose Dr. Gilbert V. Levin, inventor and holder of more than 50 patents, is an environmental engineer with a Ph.D. from Johns Hopkins University. In 1967, Dr. Levin founded Biospherics, Inc., a bioengineering firm which has since blossomed into a multi-disciplined entity whose main theme is innovation. Most recently, Biospherics (now Spherix Incorporated) announced the development of a revolutionary new low-calorie sweetener, tagatose, which is expected to hit the food market with a bang in 2003. FoodTechSource spoke with Dr. Levin, who invented the life detection experiment placed aboard the 1976 Mars Viking 1 and Viking 2 landers, for a glimpse at the processes involved in developing such an innovative product and bringing it to market.

FoodTechSource: What is D-tagatose? Gilbert Levin, Ph.D.: Tagatose is a natural sugar which appears in nature in small quantities. Its a very simple six-carbon sugar, or hexose, that is nearly identical to the six-carbon hexose fructose. It differs in that it is inverted at one carbon centerthe hydroxyl ion is on the opposite side, as is the hydrogen ion, from the molecular configuration of fructose. And this conveys to it the characteristic that it is not wholly metabolized by humans. Or any animals. FTS: It tastes sweet, like sugar? Levin: Yes, it is a sugar and it does taste like sugar; it is 92% as sweet as table sugar so it makes for essentially a 1:1 substitution. The big advantage of it is that it is of the same bulk as table sugar. The sweeteners that are generally in use now as low calorie sweeteners are high-intensity sweeteners. A tiny pinch supplies all the sweetness that is required. Thats fine if youre making beverages, in which case the bulk is supplied by water. But if youre baking a cake, where the bulk is say 35% sugar, you cant make it by just adding a little pinch of something. So we will be addressing those markets which are relatively unaddressed now: baked goods; chocolate candies, which are 50 to 60% sugar; gum, which is 50 to 60% sugar; catsup, which is 35% sugar; ice cream; frozen desserts; pies; anything where the bulk of sugar is an important ingredient. FTS: How did your company first become interested in the development of tagatose? Levin: One of the early projects at Biospherics was the development of an experiment for NASA to look for microbial life on Mars. And this experiment did fly on the 1976 Viking missions. In the course of developing the experiment I had to design a nutrient which we were going to squirt onto Martian soil and then see whether there was a reaction. The production of gas indicated metabolism. In developing that nutrient I first looked at the conventional form of glucose as an ingredient because every living thing we know of eats glucose. Then it dawned on me: suppose Martian bugs, if they exist, are different from Earth bugs.... The glucose we eat and metabolize is all the D-, or right-handed, configuration. But there is a left-handed version of the molecule, known as L-glucose, which exists but which life forms on Earth do not metabolize. So, I thought, Boy, I better send both kinds of glucose to Mars to make sure I dont miss any life that might be there. And while developing that it occurred to me if we cant digest L-glucose, and if its sweet, maybe it could be used as a low-calorie sweetener for humans. One of the early projects at Biospherics was the development of an experiment for NASA to look for microbial life on Mars.

FTS: Can it be? Levin: It turns out that L-glucose would be excellent as a low-calorie sweetener, as would some of the other L-sugars we hold patents on. But we were never able to make it cheaply enough to think about a commercial market. FTS: When did you stumble across tagatose? Levin: At about that same time we realized how closely D-tagatose resembled L-fructosewhich was also a good candidate but we couldnt make that cheaply, either. So, we decided to try D-tagatose, and we found in rat feeding studies that it was very, very low in caloric content. We secured a patent in 1988 and continued development on our own until 96, when we licensed the process for use of tagatose in foods and beverages to a Danish company. On April 11, 2001, they obtained GRAS (Generally Recognized As Safe) status for tagatose, which is required by the FDA for sales in the U.S. FTS: I understand tagatose has uses other than just with food and beverage, correct? Levin: Yes. It has multiple uses as a drug or a drug adjuvant. Principally, it seems to be very good in treating type 2 diabetes. A couple of small clinical trials were run by the University of Maryland School of Medicine using diabetics. The outcomes were quite good so we are now seeking to develop it for that purpose as well. Those rights we still retain. FTS: Are you going to be pursuing the pharmaceutical angle on this? That requires a whole different set of approvals, doesnt it?. Levin: Correct. And there you are talking a billion dollars and ten years investment. Were looking for some big partner to take that on. FTS: Expenses of a billion dollars?! Levin: Thats what a typical drug development cycle runs. It could run somewhere between $500 million and $1 billion and take up to ten years. All the studies, the safety evaluations, the clinical trials to show efficacy; its a very big deal. FTS: What about marketing D-tagatose as a nutriceutical? Levin: It will be an excellent nutriceutical and we have convinced our licensee to sell it as such. Diabetics can eat it without experiencing any rise in blood sugarfor the first time they will have a real sugar they can eat. It also protects against spikes in blood sugar levels even if a diabetic eats something containing glucose hours laterthat was shown in the University of Maryland studies.

We are also looking at its use to preserve human organs, such as the liver, during transplant. You have to store these organs, and in studies that were done at ETH, the Swiss Federal Institute, D-tagatose was shown to protect liver cells against attack from heavy metals and very toxic materials. So, the inventor has filed for a patent on that, and we obtained an exclusive license. Diabetics can eat D-tagatose without experiencing any rise in blood glucose levels.

FTS: Goodness.... Anything else? Levin: Well, we just today received notice of allowance for a patentwhich we will surely geton the use of tagatose to increase fertility and to produce heavier fetuses. This is based on tests done with ratsthose taking D-tagatose had larger fetuses, and a higher number that were viable, than those which did not take it. FTS: Is this a nutriceutical application? Levin: No, this would be a pharmaceutical application. It would be prescribed under a doctors care and it would be an extremely high dosage. The normal dose that youre going to eat in your candies and cakes would not apply here. FTS: That is quite a long series of claims. Levin: There is more. The Danes have discovered that tagatose is a prebioticmeaning it fosters so-called good microorganisms in the intestines and decreases the population of bad ones, such as E. coli O157:H7. It aids the digestive process. In addition, it produces short chain fatty acidsin particular butyrate, a naturally occurring compound that has been cited in several publications as fighting against colon cancer. Understand, we are not making that claim, but nonetheless tagatose produces butyrate and people have made such claims for butyrate. FTS: So, it has tremendous promise as a nutriceutical? Levin: Yes. And we had some trouble initially convincing our licensee to look at that because when we first began the research, nutriceuticals had a bad name. But now everybodys into them. FTS: What problems, if any, have you encountered during the development of this product? Levin: Well, I would not say it was a problem, but our licensee took a very conservative route to obtain GRAS status for its product. They appointed an internationally renowned group of scientists to form an expert panel to review the data. And they not only provided the panel with all the data we had developed over a ten-year period, but made many new studies. And, of course, we made our studies on humans at the University of Maryland available, which I think was the first time any sweetener actually had human studiesthe FDA doesnt require human studies for foods. So, Arla Foods took a very long path, but it was worth it because normally when a unique food product like ours is introduced it comes under attack. Arla wanted to be in the strongest possible defense posture to say, no, weve done all the testing and so on. FTS: Was there a reason you went overseas for the licensing deal? Levin: Yes. We couldnt get any American companies to take it on. American companies are geared toward short-term growth. They immediately thought it would mean at least a five-year development period, and most CEOs are only in for five years, with their retirements geared to their profitability. So, a lot of them think why should I do this for the next guy? FTS: It didnt have anything to do with going up against Monsanto? Levin: No, I gave Monsanto an opportunity and they declined it. FTS: So, you havent run into any problems with people suggesting it is just another sweetener and Monsanto is too big to mess with? Levin: Oh yes, we had this guy on Barrons who came out with an editorial against it when we first got our patenthe said its ridiculous, a phony balloon, we dont need another sweetener because weve got aspartame...he didnt understand were talking about a whole different market from aspartame, and a much larger market in baked goods. Tagatose addresses a much larger market than aspartameyou cant bake a pie with NutraSweet!

FTS: What is the difference between aspartame and tagatose? Levin: You just cant make a pie with NutraSweet! You cant make ice cream. If you do you need another bulking agent to take the place of the sugar you are keeping out. And there is only one bulking agentpolydextrose, by Pfizerand it hasnt been very popular because it has an aftertaste. FTS: Is that the aftertaste people complain about with Nutrasweet? Levin: No, aspartame has an aftertaste of its own, as well. FTS: So, basically then, aspartame and tagatose have different attributes which lend themselves to different markets. Levin: For the most part. However, we never thought this product could be used in soft drinks because on an equal sweetness basis it is much more expensive than aspartame. But the Danes did some experiments and they found out that if you take a tiny bit of tagatose and place it into these diet sodas made with aspartame, it makes the cola taste better. So, they filed for a patent on the synergy of tagatose with the high-intensity sweeteners and they have gotten considerable interest on the part of several major soda manufacturers. So it looks like we will compete with them in that market, as well. FTS: How important was it for you to obtain GRAS status? Levin: It was very important, because even though we knew we were going to get the GRAS, the Danes would not commit to building a manufacturing plant until GRAS were obtained. So now with that having happened, they are moving forward with their plans to commercialize. You cant sell it until you build the plant and make it. FTS: When do you expect that to take place? Levin: It is our hopewe cant really predict what they are going to dowe will be on the market within about two years. FTS: What is involved in going from the R&D stage to the production stage? Levin: What we did, as soon as we signed a tentative licensing agreement with them, we went over to Denmark and helped them construct a pilot plant. We designed it and had our guys help them put it up. They ran the pilot plant for a year before they decided they were really going to sign on, firmly. It was a question of optimizing the process to go from pilot-scale production to full-scale. They have fully designed the plant now, they have also located a site where they are going to put it. Were just anxious for them to go ahead and start the brick work. FTS: Will you be marketing overseas? Levin: Now that they have GRAS in the US they are going ahead to get GRAS, or its equivalent, in all the major European countries and around the world. FTS: Do you expect they might run into problems with the European Union regulations? Levin: I think the EU is developing regulations essentially the same as the FDAs. But in addition there is a European Committee on Food Additives; it will meet in June and at that time will consider making a recommendation on tagatose. FTS: Spherix is obviously very firmly entrenched in biotechnology. Whats on your horizon? Levin: A very bright future. We are launching a new product called FlyCracker, which is a safe-for-humans pesticide. Its being marketed now for use against flies in stables, barns, food processing plants, poultry plants...any enclosed-environment plant. This is a simple powder that gets sprinkled around the periphery of the area and prevents any fly larvae from pupating, so that no eggs develop. We think it is a very important product because it is perfectly safe for humans and for the animals. We have developed expertise in small molecule carbohydrates; theres a theme to our biotech program.