It shows a practical example of a natural chemical drug, levodopa, can have impurities without unknown brand-new toxic and never-tested synthetic chemicals present. It is reprinted from My Life & Rollercoaster Career. “Chapter 4. Adulthood in America,” below:
“LEVODOPA EXTRACTION AS EXAMPLE OF THINKING OUTSIDE THE BOX
It was around mid-1970 when I was working for Dr. Madis Laboratories that has since changed hands a few times. The owner, Dr. Madis, had hired a new plant manager Mr. Guy Riccardi. Guy brought with him a process for making levodopa (l-DOPA) from velvet beans. For your information, levodopa was a new drug for treating Parkinson’s Disease (PD) at that time. But it had some serious toxic side-effects that were allegedly caused by impurities present in the synthetic chemical which could not be removed during its purification process. According to Guy, Dr. George C. Cotzias, a pioneer in using levodopa in treating PD, had done some preliminary study with natural levodopa from velvet beans and found it to have much fewer side-effects than its synthetic counterpart; and he was interested in a source of the natural levodopa.
Guy’s process made use of the reverse osmosis (RO) process to purify this product. The RO process involves the use of a membrane (like a microscopic sieve) of appropriate size through which water and small molecules like levodopa can pass but not large chemicals like protein and carbohydrates, among others. The water solution/filtrate that contains the levodopa can then be easily purified. At that time, RO machines were very expensive. So Dr. Madis asked me to look into an alternative method of isolating levodopa from the beans. I started with literature search and found a couple of patents but none of them worked. One of the better ones actually ended up making a soup and it was very complicated to separate levodopa from it. So, I designed a few experiments for my chemist to try. At the time the only chemist I had was Bob Noll. He was basically an analytical chemist, and a good one. After a few failures playing with messy ‘soups’ an idea came to me. Why try to separate levodopa from the protein and starch soup? Why not fix or trap the big molecules within the beans before even starting to extract the beans with water so that we would have only water and smaller chemicals without proteins or carbohydrates to deal with. So we didn’t mill the beans. Instead, we simply cracked the beans into pieces or a very coarse powder and thoroughly wetted and mixed the beans with acetic acid to denature the proteins. That mixture was simply a damp mass not a mash or suspension. Then, when we poured water into the vessel with the beans and warmed them up to fix the proteins in the beans, there was no more mess. What we got was a regular extract and not a bean soup. After we filtered and concentrated the extract for crystallization, we tested the crystals of levodopa. What we found was a very pleasant surprise. The purity was already over 90%. The time we spent on this project was maybe only three weeks. Since the beans are known to be toxic only because they contain the levodopa, the chances that the purified natural levodopa containing a highly toxic chemical other than levodopa would be slim as opposed to a synthetic levodopa produced from unnatural chemicals reacting with one another to produce totally unknown and potentially highly toxic intermediate compounds that may have never existed in nature before. During my 55 plus years of working with chemicals, the conventional wisdom among chemists is that the synthetic version and the natural version of a chemical are the same as long as they are both pure. But how pure? 98.0% or 99.9%? How about the remaining 2.0% or 0.1% containing a tiny amount of some highly toxic unknown chemical? The USP/NF specifies the purity of levodopa to be containing 98.0% to 102.0%, depending on the analytical methods used. It doesn’t specify 100.00% or even 99.99% (absolute purity or close to it) because the analytical techniques available are not that precise. So, a ‘pure’ chemical always has impurities in it. The impurities in natural chemicals are not brand new to our environment. But those present in synthetic chemicals are totally unknown to us and have absolutely no history of interacting with us. I think you should be aware of these facts.
I suggested to Dr. Madis that we patent this process. He agreed and I wrote up the process. My memory is that at that time you couldn’t put just any person’s name on the patent. This person had to actually have taken part in coming up with the idea or had worked on developing it, not just being the owner of a company and you are then automatically entitled to put your name on the patent application. Otherwise, the patent would be disallowed if others contested it. So, since Dr. Madis’ name was not on the application, he simply shelved it. And I have never heard anything more about this project since. However, Guy knew about this process and the simple rationale behind it.
After I was later fired from Dr. Madis Labs for another matter, I heard rumors that Merck had started a levodopa production facility in Brazil to make the product from velvet beans. I was aware that Guy had been in touch with Merck. But I don’t know if the reason of his contact with Merck was for levodopa production or for seeking employment. I always wonder if the rumors were true, and if so, whether Merck used Riccardi’s RO process or my protein-fixing process. If it is true, I bet it is the latter – a much superior and simpler process.
I have described traditional Chinese herbal medicine more than once or twice before as rich sources of natural cosmetic ingredients in this memoir, in my Newsletter (LCHN) to be republished simultaneously with my memoir, in my Encyclopedia, and elsewhere. In the Encyclopedia, I actually added a whole section on Chinese cosmetic ingredients in its 2nd and 3rd editions published in 1996 and 2010 respectively. For people who never had experience or knowledge of Chinese herbs, many of them are turned off by the use of esoteric language in describing their properties. But if you know Chinese herbs and also have been trained in the sciences dealing with them, you can correlate archaic or esoteric language with modern scientific (including pharmacologic) terms. I did just that and figured out some secrets hidden in that ‘mumbo jumbo.’
Hence, during my last consulting period between 1970’s and 2000’s, I consulted for many cosmetic and drug companies, including Avon, Estee Lauder, Roche, and L’Oreal, among others. The most memorable experience was with Avon. Its new facial treatment cream contained retinoids (related to Vitamin A). It was one of its best sellers; but it had a problem. It caused rashes and needed that fixed naturally and fast. There was no time to perform basic R&D. There were some big names in the industry at the time, including a well-known dermatologist Dr. Kligman and a Ph.D. in Pharmacognosy known around the world (see Chapter 8: David versus Goliath: NCI SBIR Phase II Database Contract – What if…?). So Avon started interviewing consultants. As far as I was told, it only interviewed three altogether – the above two, plus me.
In my presentation, I told them I could first give them five herbal extracts for them to test against rashes, and one of them should work. So, I was given a 3-year contract. Probably the conservative thinking of Avon’s technical staff that that research would require years and not months. However, in only weeks, I gave them the five extracts. One worked. It was a magnolia flower bud extract. Avon wanted it right away. Since I was not an approved vender at the time, we had to go through one of Avon’s approved vendors so that there would not be any delay in supplying them with the extract. That seemed to have solved everyone’s problem. Avon was happy; so were its approved vendor and I.