How To Make AL 721

Published in SAN FRANCISCO SENTINEL, January 30, 1987; also published as AIDS TREATMENT NEWS #24, same date.


UPDATE April 28, 1987: For more recent information, see AIDS Treatment News #30, "AL 721 Workalikes: Where To Get Them", April 24, 1987. Issue #30 includes a warning against suddenly stopping use of AL 721.
Since this issue (#24) appeared, the "home formula" has come into widespread use. But we don't know of anyone who has used the more difficult "laboratory formula". Instead of extracting AL 721 directly from egg yolks, it seems more
practical to buy the ingredients, such as egg lecithin, from companies which specialize in such products.


*********************

Five weeks ago I published a report that Americans could receive treatment in Israel with AL 721, an experimental
AIDS/ARC medicine developed in that country at the Weizmann Institute of Science. Since that time the research project
which accepted Americans has been shut down, as a result of pressure from within the U.S., so the treatment is no longer
available.

What is the politics behind this shutdown of AIDS research and treatment? Not only have individuals lost a treatment
option, but also the highly esteemed immunologists working at Weizmann have lost learning opportunities. The political
answers are unclear, but the following sketch, which we have not been able to confirm, seems to reflect the understanding of those close to the situation:

* The patent licensee which owns the rights to AL 721 in the U.S. and many other countries is Praxis Pharmaceuticals,
Inc., of Beverly Hills, CA. Tiny by drug-industry standards, this public company has only six employees, according to its
"10-K" disclosure form. This company strongly objected to the use of AL 721 in Israel to treat American patients.

How can a U.S. company shut down some of the AIDS research at the world-famous Weizmann Institute? Why can't the public policy of the United States find a way to make an exception to business as usual during the AIDS emergency?

* Praxis is seeking approval from the U.S. Food and Drug Administration (FDA) to market AL 721 for AIDS and other
diseases. But this small company faces an uphill fight because much larger and more influential corporations have their own AIDS treatments on the Federal agenda. Apparently there are important Federal officials who want AL 721 to never be approved, because they are committed to other treatment approaches instead. The owners of Praxis are apparently very concerned that any protest or publicity, such as could be generated by Americans traveling to Israel to receive treatment there when it is unavailable here, could deprive them of the allies they do have in the FDA, and kill the AL 721 treatment regardless of medical or scientific merit.

Praxis has been outspoken in telling Congress about certain problems in the Federal management of AIDS research,
and it may have suffered as a result.

* It is believed that there is no chance whatever for FDA approval until well into 1988 -- over a year from now -- even
though the medicine is known to be completely safe and there is nothing to lose by trying it.

If the above reports are true, then all the communities concerned with AIDS have a decision to make. Should we put
this issue on the public agenda to try to change national policy, to demand that saving lives be given a higher priority,
or keep quiet to avoid risking further damage to AIDS treatment research and development?


AL 721 Quick Background

AL 721 was first developed at Weizmann as a medicine for other diseases, long before its possible relevance to AIDS was known. The U.S. patent (number 4,474,773, October 2, 1984) does not mention AIDS. AL 721 may be the first of a new class of medicines using what has been called "membrane engineering" -- modifying cell membranes to achieve treatment goals. AL 721, which consists entirely of a mixture of three lipids (fats) found in ordinary food, increases the "micro fluidity" of cell membranes, by increasing the ratio of phospholipids to cholesterol. Increased membrane fluidity makes it harder for viruses to attach to receptor sites and enter the cell.

The meticulously careful and thoroughly documented scientific work which developed the theory behind AL 721 is
illustrated by the 2-volume book Physiology of Membrane Fluidity, edited by Dr. Meir Shinitzky, a cancer researcher at
the Weizmann Institute and the principal developer of AL 721, and published by CRC Press, Boca Raton, Florida.

The first reference to AL 721 and AIDS was in a letter to the New England Journal of Medicine, November 14, 1985, by
several researchers including Robert Gallo, M.D. and Dr. Prem Sarin of the U.S. National Cancer Institute. The letter
reported that AL 721 could prevent the infection of human T- cells by the AIDS virus in the laboratory. (For more
background and references, see my technical article published April 1986 by the Documentation of AIDS Issues and Research Foundation, San Francisco; to obtain a copy, send a self- addressed stamped envelope to this writer at the address below.)

Theory suggests that in addition to AIDS, AL 721 might also help against other lipid-coated viruses, such as herpes,
CMV, and Epstein-Barr. It was found to be effective against herpes in one animal test, reported October 1986 at a symposium in New Orleans.

Since AL 721 had been known to be safe and had previously been tested in humans in Israel, it would seem that the
encouraging laboratory results with the AIDS virus would quickly be followed by clinical tests. But in the 14 months since the laboratory report was published, we only know of eight people who have received AL 721 in clinical trials, all mildly ill lymphadenopathy patients at St. Luke's/Roosevelt Hospital Center in New York. The results were encouraging, with large reductions in viral activity (about 80 percent) in five of the seven patients for whom measurements were available. Tests with AIDS patients are now about to begin. (We had heard that this study was full, but now it is rumored that it may be expanded. We don't know whether or not a placebo will be used.)

One person who was near death from AIDS a year ago and is now in good health after AL 721 treatment wrote about his experience (AIDS Treatment News January 2, 1987). The treatment works slowly; it took two weeks to feel any effect,
and months before T-cell counts rose significantly. Probably the treatment must be continued indefinitely.

The picture emerging is that AL 721 can be effective as an antiviral for many people, but that therapy might be improved by also using an immune treatment, such as a thymus hormone, after the virus infection had been slowed or inactivated.

AL 721 is not a cure, not a magic bullet, although it probably can save lives and restore many people to health.
Since there are no dangers or drawbacks to AL 721, there is no justification for stopping people who want to use it.


AL 721 Formulas

We publish the following to open doors.

There are three approaches to making AL 721: a laboratory formula, a substitute which can be made at home, and new methods likely to be available soon.

AL 721 is easy to make in a laboratory, but companies cannot do so openly because they could be sued for patent
infringement. Also, no useful instructions for making the substance have previously been published. The U.S. patent, and also a published scientific paper, give two different procedures for making AL 721, but neither of them is useful in
practice. So this writer obtained professional assistance in expanding the sketchy instructions disclosed in the patent into the formula given below (see box). The patent applies in many but not all nations, so it would be legal to make AL 721 in some countries, and legal to advertise openly that Americans or others could go there for treatment. No one has yet set up such an operation as of this writing.

The substitute home formula (see box) was developed by a chemist in the New York City area in January 1987, and
distributed at AIDS support meetings there. It is made by mixing butter or cooking oil with a concentrated lecithin
formula widely available in health-food stores and in some drugstores. The proportions of the three ingredients of AL 721 -- phosphatidyl choline, phosphatidyl ethanolamine, and neutral lipids -- are not exact but are well within the range of at least one set of specs for the official product. However, there are slight chemical differences between ingredients
derived from eggs (used in AL 721) and those from the other sources used here. There is no known reason why this home substitute could not work like AL 721. Every expert I have spoken to suspects that it probably will work, at least to some extent; but nobody has proven that it will.

The third approach is based on special food products not yet entirely available. Just before press time, this author
learned of a suitable egg lecithin now being sold in the United States at a reasonable price ("Phosphatidyl choline 60 percent from egg yolk", which also contains about 30 percent phosphatidyl ethanolamine); but unfortunately the chemical company which sells it does not allow any of its products to be used for human consumption.

Neutral lipids would need to be added; butter or cooking oil could be used as in the home formula. But it would be
better to obtain neutral lipids from egg yolks as described in a scientific article on AL 721 (Lyte and Shinitzky, "A special
lipid mixture for membrane fluidization", Biochimica et Biophysica Acta 812, 1985, 133-138). When food companies can
supply both the egg lecithin and the egg neutral lipids, which would be entirely legal to do and technically easy, then it
will be possible to make a product virtually identical to AL 721 in anyone's kitchen.

There are no known problems in combining this food with any other AIDS drug or therapy.

AL 721 should be stored frozen, and moved to the refrigerator a few hours before use. It should not be allowed
to stand at room temperature, as the components may separate; for best absorption they should remain well mixed when the product is used. AL 721 should be taken on an empty stomach, preferably in the morning and/or evening, with little or no fats eaten for at least two hours afterwards. Each dose is 10 grams of the lipids.

Patients should discuss any treatments they are using with their physicians. At this time few physicians are familiar
with AL 721. For a review of scientific and medical studies concerning this treatment, send a self-addressed stamped
envelope to John S. James, P.O. Box 411256, San Francisco, CA 94141.


AL 721 Laboratory Formula

Caution: the process below uses highly flammable materials and must be done with proper facilities. This is NOT a home recipe.

We have combined this information from many sources, and have NOT TESTED the version written here. We publish this information as a starting point for professional development, NOT as a guaranteed method ready for use.

Use of this formula in the United States, and in some other countries, may infringe patent rights.

1. Dissolve 4 grams of tocopherol acetate (vitamin E) in 40 ml of ethanol, add this to 40 liters of acetone and combine
with 20 liters of hen egg yolks. Mix five minutes at room temperature. We believe that dried yolks can be used.
2. To the solid material produced in step 1, add 40 liters of acetone and 800 ml aqueous solution of 0.1 M CaCl2 and 0.1 M MgCl2. Bring to 47 degrees C for one hour, while mixing thoroughly. Filter WHILE HOT, and discard the solids.
3. Cool to -20 degrees C for at least 16 hours; the AL 721 precipitates. Filter with a metal mesh, discard the liquid.
Transfer the product to an evaporation vessel of about 5 liter capacity, and mix with 4 grams of tocopherol acetate dissolved in 40 ml of ethanol. There should be 1.5 to 2 Kg total at this step.
4. Evaporate the solvent in the 5 liter flask by using a water pump for 1-2 hours, then an oil pump for 2-6 hours. In
the final step, put the container in a water bath at 40 to 50 degrees C., to help in evaporating the solvent. Mix the final
product well. About 1 to 1.4 Kg of AL 721 should be produced -- enough to last one person for at least 50 days.
5. Quality control:
a. The final product should contain about 70 percent neutral lipids (including 2 to 4 percent cholesterol), 20
percent phosphatidyl choline, and about 7 percent phosphatidyl ethanolamine. At room temperature the product will separate into two phases, with the neutral lipids on top. Part of the upper layer can be removed if necessary to adjust the proportions.
b. Acetone in the final product should not be more than 300 ppm.
c. To help avoid bacterial contamination, pasteurized egg yolks are used. Store the product at -20 degrees C.


AL 721 Substitute (Home Formula)

The following instructions have been distributed at PWA meetings in New York. The text has been slightly changed here. More information is available by calling the phone number below.

PC-55 (tm) is a high-strength lecithin concentrate made by Twin Laboratories, Inc., Ronkonkoma, NY. It contains two of the three ingredients of AL 721; they are in a 5:2 ratio, close to the 2:1 used in AL 721. Neutral lipids can be added to PC- 55 making it a membrane fluidizer comparable to AL 721. This material is a food nutrient, it is not a drug. It is safe.

Combine five tablespoons of PC-55 and 12 tablespoons of water in a bowl, and whip with an electric mixer or blender.
Slowly add 6 tablespoons plus one teaspoon of butter which has been melted (measure the butter before melting). Whip thoroughly three to five minutes. This mixture divided into ten even doses gives slightly over 10 grams of the lipids per dose. Each dose should weigh about 30.4 grams or 1.06 ounces.

The individual doses can be placed into plastic sandwich bags for freezing. If you don't have a scale, you can measure out two tablespoons to each bag, then add a much smaller amount to divide the remainder. One person separates the doses in an ice-cube tray. Move each dose from the freezer to the refrigerator a few hours before use. This preparation spoils very rapidly at room temperature; it must be frozen unless used immediately.

(An earlier version of this formula used cooking oil instead of butter. The proportions are 5 tablespoons PC-55, 5
tablespoons + 1 teaspoon oil, and 10 tbsp water.)

The material is best eaten in the morning, spread on fat-free bread or mixed with fruit juice. The user should eat a
fat-free breakfast which might consist of fat-free cereals, skim milk, fruits, or vegetables. There are no restrictions on
lunch or dinner. An additional dose might be taken before going to bed. Patients treated in Israel are given two doses a day for about four weeks, then single doses for most of one year. Some people with AIDS might experience diarrhea with this membrane fluidizer, especially with the additional dose. Eat brown rice and other solid foods.

You can help others and yourself by keeping a record of your experience -- doses, dates, and any resulting effects.

For information call Steve Gavin, 201-677-2795.