PETER J.

D'ADAMO

Originally published in the Townsend Letter For Doctors, August 1990

Copyright 1990-2009, All rights reserved

Introduction

Lectins are proteins commonly found In foods of high nutritional value. Typically,
lectins interact with glycoprotein, glycolipid or oligosaccharide residues on the
cell surface, causing a variety of effects including: blastogenesis (rapid cell
reproduction), agglutination and receptor agonism. The mucin-rich gut wall is
especially prone to direct reactions with lectin-containing foods in the diet.

Lectins (from the Latin legate, to pick or choose) were first identified in 1888 by
Stillmark at the University of Dorpat in Estonia. While investigating the toxic
effects on blood of castor bean extract (Ricinus communis) he noticed that the
red cells were being agglutinated. He isolated the material responsible for the
agglutination and called it ricin. Shortly afterward at the same university Helfin
discovered that the toxic extract of the seed Abrus precatoris also caused cells to
clump together. This new agglutinin was called abrin. This immediately caught the
attention of the German bacteriologist Ehrlich who recognized that he could
investigate certain immunologic problems with them rather than the then popular
bacterial toxins. With these two agglutinins some of the most basic principles of
immunology were discovered, such as antibody specificity and species specificity.
In 1908 Landsteiner reported that small amounts of lentil lectin would agglutinate
rabbit erythrocytes, even high concentrations of the lectin had no effect on
pigeon red cells.

The first lectin to be purified was concanavallin-A, isolated from the jack bean. In
1936 Sumner and Howell noted that the addition of Con-A to a solution of glycogen
caused the sugar to precipitate, and that the agglutination of red cells by this
lectin was inhibited by cane sugar. They suggested that the hemagglutination by
Con-A might be the consequence of a reaction between the protein with
carbohydrates on the surface of the red cells. In other words lectins bind sugars,
and they agglutinate cells by means of this binding. For example the agglutination
of red cells by Con-A specifically inhibited by the sugars mannose or glucose,
Indicating that Con-A binds mannose and glucose on the cell surface. It was soon
discovered that lectins not only agglutinate red blood cells, but also other kinds of
cells including lymphocytes, spermatozoa, bacteria and fungii.

There is some controversy over whether non-agglutinating (i.e. monovalent)

molecules having high affinity for carbohydrate should be termed "lectins",
however in this monograph they have been included, as many of these molecules,
while not agglutinins, do have mitogenic propertles. In 1945 William Boyd of the
Boston University School of Medicine discovered that lectins can be blood group
specific; being able to agglutinate the red cells of one type but not those of
another. He discovered that lima bean lectin would agglutinate red cells of human
blood type A but not those of O or B. The seeds of Lotus tetragonobolus can
agglutinate group O specifically, and Bandairaea simplicofolia is specific to group
B. The specificity of lectins is so sharply defined that they can differentiate
among blood subgroups. Dolichos biflorens lectin reacts more vigorously with
blood group Al than A2. Other blood groups can be distinguished by lectins, such
as M and N types, and lectins can help distinguish and diagnosis "secretors";
people who secrete glycoproteins that have blood-group specificity into their
urine, saliva and other body fluids

Molecular Biology

Carbohydrates are the most abundant group of biological compound on the earth,
yet comprise only about 1 percent of the human body. Nevertheless approximately
50% of the dietary caloric intake is in the form of carbohydrate. Structural
carbohydrates are usually glycoconjugates such as glycoproteins and glycolipids.
Monosaccharides rarely exist free as such in nature. Typically they exist in giant
molecules called polysaccharides that can consist of up to 26,000
monosaccharides. Sugars also appear frequently as oligosaccharides made up of
from 2 to 10 monosaccharides.

Until recently, it was not recognized that nature could employ sugars for the
synthesis of highly specific compounds that can act as carriers of biologic
information. Monosaccharides can serve as "letters" in a vocabulary of biologic
specificity, where the words are formed by variations In the nature of the sugars
present, the type of linkage, and the presence or absence of branch points. The
first proof that sugars could serve as specificity determinants came from the
discovery that influenza virus could agglutinate red cells only In the presence of
the membrane bound sialic acids. It these were removed, the virus no longer
binds to the cell. Removal of sialic acid exposes the terminal underlying galactose
unit and results in the rapid clearance of the treated cells from the bloodstream.
Sugars on cell surfaces also seem to determine the distribution of the circulating
cells within the body. Radioactively treated rat lymphocytes will migrate to the
spleen when re-injected into the animal. However if the sugar fucose is removed
from the surface of the cells before reintroduction, the cells migrated to the liver
instead, as if "the fucose served as a ZIP code- directing the calls where to go." It
was not until 1953 that Morgan and Watkins demonstrated that the specificity of
the ABO blood group-system was determined by sugars. For example, the
difference between blood types A and B lies in a simple sugar unit that sticks out
from the end of a carbohydrate chain of a glycoprotein or glycolipid. In blood A the
determinant is acetylgalactosamine and in group B it is galactose.

Several toxins of bacteria and plants are known to recognize carbohydrate

structures present in various classes of cell surface molecules.

When a lectin contains multiple binding sites, they can interconnect large
numbers of cells, causing them to clump together or agglutinate. Each molecule
of a lectin has two or more regions, perhaps clefts or grooves, each of which fits a
 complementary molecule of a sugar or several sugar units of an oligosaccharide.
It is by means of these combining sites that the lectin attaches itself to the
sugars on cell surfaces.

PROPERTY
Specificity for human blood
groups
Toxicity in animals and humans
Induction of mitosis in
lymphocytes
Agglutination of malignant cells
Precipitation of polysaccharides
and glycoproteins
Binding of sugars
>Table 1. Properties and uses of lectins.
APPLICATION
Blood typing; structural studies of
blood group substances;
identification of new blood types;
diagnosis of secretors.
Studies of nutritional value of
foodstuffs
Studies of chromosomal
constitution of cells.
Investigation of architecture of
cell surfaces.
Isolation, purification and
structural studies of
carbohydrate-containing polymers
Studies of specific combining
sites on proteins

The binding of lectins to sugar is quite weak. It does not form a covalent bond, but
is reversible, like enzyme-substrate or antigen-antibody reactions. Lectin-sugar
reactions actually share many factors in common with antigen-antibody reactions,
especially precipitation, which has prompted several investigators to suggest that
lectins are plant antibodies. However this has been tempered by several major
differences between the two. Antibodies are made by higher organisms which
have specific immunologic organs. Lectins are present as constituent proteins.
Second, antibodies are all structurally similar to one another, whereas lectins are
structurally diverse; examination of the amino acid sequence, molecular size and
other molecular properties show that lectins have little in common other than
they are all proteins. For example soybean agglutinin is a glycoprotein with no di-
sulphide bond; its molecular weight is 120,000, It consists of four subunits and
has two binding sites. Wheat germ agglutinin is not a glycoprotein and is rich in
di-sulphide bonds with a molecular weight of 36,000, It has two identical subunits
and four binding sites for sugars.

Effects of Lectins in the Diet

Lectins are apparently most widely distributed in plants, where they were found in
almost 1000 plants of some 3000 examined in recent years. They are particularly
abundant in legumes and they account for between 1.5 and 3 percent of the total
protein content of soy and jack beans. The second most common source of lectins
are seafood.

Although many lectins are destroyed by normal cooking (which is why grains and
beans are edible), many are not. Relative resistance to lectins was pan of the
classic description of wheat germ agglutinin (WGA) made by Aub in 1963. WGA as
Freed points out is in fact one of the more heat sensitive lectins, being destroyed
after 15 minutes at 75 degrees C, whereas other wheat lectins in gluten and
gliandin resist autoclaving at 110 degrees C for 30 minutes. Gibbons and Dankers
noted that in over 100 food plants found to contain active lectins, seven were
autoclave resistant (apple, carrot, wheat bran, canned corn, pumpkin seeds,
banana and wheat flour). Nachbar and Oppenheim also noted high levels of lectin
activity in dry roasted peanuts, Corn Flakes, Rice Krispies, and Kellogg'sSpecial
K. The banana agglutinin was actually enhanced by heating, and was inhibitable
by n-acetyl glucosamine (NAG) and N-acetylgalactosamine (blood group A antigen)
glycoproteins. Phytohemagglutinins from kidney beans can resist mild cooking
and retain lectin activity even at 90 degrees C for 3 hours. Pre-soaking the beans
however resulted in complete loss of lectin activity. Several investigators noted
year-to-year and batch-to-batch variations in the lectin content of foods, so the
occasional lectin is likely to occur even with foods normally considered safe.

Mucotractive effects of lectins

It has recently been shown that Con-A causes a greatly enhanced secretion of
mucous from the intestines of laboratory rats. It has been suggested that this
"mucotractive" effect of lectins may have some usefulness in cystic fibrosis. DJ
Freed ingested a 10mg dose of Con-A in tap water. Later that day and on the next
day he experienced moderate by quite intrusive bowel colic, with passage of foul
smelling flatus of unfamiliar odor, and on day three passed a stool of normal size
and texture, but thickly coated with mucous. Brady gave purified WGA to human
volunteers and recovered about 2% from the feces. It was speculated that the
lectin escaped digestion by binding to the dietary fiber, and noted that a high fiber
diet is also, by and large, a high lectin diet.

Lectins which are especially rich in di-sulphide bonds such as WGA are very
resistant to proteolytic enzymes, detergents, urea, alkalis and acids. Foodstuffs
are naturally rich in fiber Important cause of allergies. Dietary lectins also
stimulate mast cells which can degranulate and release stored histamine, leading
several researchers to ascribe a role for dietary lectins in the genesis of food
allergy. However it is not generally known why some individuals become
sensitized to food in their diets. In an attempt to clarify this, coeliac disease has
been extensively studied, since patients with this disease usually normalize when
placed on a gluten free diet. Researchers reported that the mucous membranes of
coeliac patients showed sugar residues which were capable of binding to the
lectins in wheat germ, which resulted In a cytoxic reaction. Rats treated with
Concavallin-A or wheat germ lectin developed a gut membrane that was
paradoxically impermeable to small molecules, but very permeable to large, highly
allergenic molecules, a situation which is mimicked in food allergies and coeliac
disease.

A component of wheat gliandin has been shown to bind preferentially to crypt

epithelial cells of coeliac disease subjects, but only rarely in health volunteers.
This seems to result from an Immaturity in the pattern of call surface
carbohydrates on the coeliac enterocytes, perhaps, as Kottgen speculates, due to
a genetically determined deficiency of a growth dependent enzyme, N-acetyl-
glucoaminyltransferase, which renders coeliac patients sensitive to the effects of
the oligomannosyl-specific lectin gluten. Mannosyl oligosaccharides have been
tried clinically, with mixed results. Several investigators have noted a syndrome
that is indistinguishable from coeliac disease that is produced by soy beans.
Investigators have also described a patient with soya intolerance whose severe
diarrhea was ameliorated by ingesting sugar inhibitors of soybean agglutinin
(SBA) such as galactose or lactose, whereas glucose or sucrose made it worse.
Ament and Rubin noted violent reaction to soy protein formula in a 6-week-old
infant. The infant developed (sequentially) fever, leukocytosis, cyanosis, vomiting,
massive blood tinged mucousal diarrhea, dehydration and acidosis. All symptoms
disappear after discontinuing soy milk. The jejunal mucosa, previously normal,
became inflamed and flat with the disappearance of the intestinal villi; however it
had regenerated by the forth day after discontinuance.

PNA has an extraordinary preference for gastrin secreting cells as opposed to

other stomach cells. WGA binds to microvilli in the intestinal crypts and to the
goblet cells with an affinity which increases from the proximal to distal intestine.
Lectins in the small intestine appear to encourage bacterial overgrowth. Lectin
damaged areas of the jejunum have been observed to be characteristically
heavily infected with coliform bacteria. It Is worth noting that most human
microbial pathogens and parasites are able to overcome normal gut motility by
lectin-like attachments of lectin like activity. Forsdyke has hypothesized that
those ingested lectins that are cytotoxic (via alternative complement activation)
are likely to damage first the lymphocytes of the mesenteric nodes, thus making
more likely bacterial overgrowth and eventual food allergy.

Jaffe classifies lectins under Type 4 Cell Activation Lectin/ Cytokine Interactions."
Various lectins have been shown to bind to IgE receptors, including pea, WGA,
peanut agglutinin (PNA) and Con-A. WGA has been shown to stimulate histamine
secretion from non sensitized rat mast cells in vivo, In the absence of
extracellular calcium. This is in accordance with other observers who noted a
bacterial lectin-like reaction in the lungs of intrinsic asthma sufferers attributed
to a defective pulmonary barrier which would allow bacterial lectins to interact
with the basophil cell surface and induce degranulation and histamine secretion.

Nachbar tested 88 common food items and reported erythrocyte agglutination

activity in 38. Many foods showed agglutinating activity so substantial that the
extracts could be diluted several fold. Crude extracts of various foods tomato,
lettuce, cucumber, wheat bran and whole wheat, sesame and sunflower seeds,
vanilla yogurt, coconut, banana and baby food banana, carrot, onion, apple, alfalfa
and soya protein have also been found to bind, and in some instances precipitate
the components of human saliva, including cellular debris and bacteria. This may
have some significance in the development of caries. Interestingly, avocadoe
lectin inhibited the sucrose dependent adherance of S. mutans to plaque pellicle.
Approximately 1 to 5% of the ingested dietary lectins are absorbed into the blood
stream. Here they can clump and bind to red and black blood cells, destroying
them. It has been proposed that much of the low grade anemias seen In the third
world may be resulting from destruction of red blood cells by lectin rich grain and
bean diets.

Other Systemic Effects

Kidney

Both human and animal kidney contain abundant structural glycoproteins that
offer binding sites for various lectins. WGA binds to the glomerular capillary wall
in man, in addition to the inner surfaces of the collecting ducts.

Lectin binding to insulin receptors

Many dietary lectins, including WGA, lentil (LCL) and green pea (Pisum sativum)
lectin (PSA) can bind to human insulin receptors and mimic insulin. WGA Is as
effective In molar terms as is insulin at enhancing glucose oxidation and has been
shown to enhance the affinity of insulin Itself for its receptors. This low dose
insulin-facilitating effect was also observed for LCA. Many workers have taken
note of the differing glycemic effects observed with various carbohydrates.
Diabetes are often prescribed a high fiber diet Including the use of pectins. The
difficulty with the mimicking of hormones by dietary lectins is that they lack the
normal feedback and metabolic degradation controls. Insulin mimicking lectins
produce more persistent effects than insulin, resulting in greater deposition of fat
and inhibition of lipolysis.

Nervous System

Human myelin has a strong affinity for ConA, WGA, PHA and LCA, as do nicotinic
acetylcholine receptors of the rat brain. Russian studies noted a subnormal
lymphocyte response to PHA and Con-A in schizophrenics.

Miscellaneous tissues

Lectins have been shown to bind to human syncythial trophoblasts, to inhibit the
binding of nerve regrowth factor to fibroblasts and to bind follicle stimulating
hormone. Multiple interactions with normal plasma enzymes, glycoproteins and
immunoglobulins have been observed.

Lectin Activity In Microbial Systems

The Thomson-Friedenreich antigen (T-antigen) is generally not found on human
cells, but can be exposed after the sialic acid molecule have been removed by the
action of neuramidlase. This can commonly occur since all Pneumococci, most
strains of influenza, Vibrio cholerae and Clostridium all contain active
neuramididase. Antibodies against T antigen are found in humans after the first
few months of life. Peanut agglutinin is specific for it. After neuramidase
exposure, PNA binding sites for T-antigen can be found on lymphocytes,
erythrocytes, breast epithelial cells, glomeruli, milk-fat globule membranes and
thrombocytes, serum glycoproteins. Hemolytic-uremic syndromes following
pneumoccocal infection, presumably an attack by anti-T antibodies, could
possibly result from T-specific lectins. It also interesting to ponder the
observation of several investigators who have noticed that many cases of food
intolerance develop after influenza.

Bacteria typically attach to prospective host cell membranes via receptors with
lectin- like sugar specificity. This is of great importance, as the adherence of
bacteria to host tissue surfaces is the initial event in a bacterial infection.
Salmonella and Escherichia coli both carry several surface lectins with
pronounced immunosuppressive ability. Both adhere to epithelial cells through
units of mannose on the cell surface. Colonization of the urinary tract with E. Coli
can markedly be reduced by the administration of mannose sugars. Inhibition of
bacterial adherence to bladder cells has been thought to account for the
beneficial effects of cranberry juice. Cranberry juice cocktail inhibited the
adherence of urinary isolates of E. Coli expressing type 1 fimbriae (mannose
specific) and P fimbrae (specific for apha-d-gal-[1-4] beta-d-gal). Pineapple juice
inhibited type 1 but not P type fimbrae. Lectins on type 2 fimbriae, which
recognized galactose receptors on lymphocytes, play a crucial role in the
phagocytcsis of several Actinomyces spp.

Irritation of the gut mucosal tract by Salmonella lectin may be as important in the
production of the symptoms of food poisoning as the salmonella food toxin itself.
In sensitive individuals, lectins in the diet can bind to the intestinal walls, causing
severe lesions, inflammation and swelling.

Neiserria gonnorhea, the bacteria which causes the venereal disease gonorrhea,
Is unique in that it is the only member of its family that is pathologic and the only
member that is agglutinated by wheat germ agglutinin.

Several lectins have been shown to possess agglutination properties against

bacterial strains. Staphylococcus aureas and mutans has been extensively
studied, These have been shown to be agglutinated by several commonly
available lectins- including tomato, cantaloupe and wheat. The author has
employed tomato lectin in clinical practice by way of topical applications of raw
tomatoes to the eyes in staphylococcal conjunctivitis with very satisfactory
results.

Lectins have been shown to inhibit the release of Myxovirus and Newcastle
Disease virus from infected cells.

Lectin-Induced Mitogenesis
In 1960 Nowell added PHA to a blood sample to agglutinate erythrocytes and thus
encourage their removal and noticed to his annoyance that the lymphocytes had
also been affected. He had discovered the mitogenic effect of PHA (and many
other lectins) which was to be the key to the explosion of knowledge about
lymphocyte physiology. Lectins are probably the best biologic response modifiers
(outside of monoclonal antibodies) found in nature.

Hemagglutinating properties are not necessary for a lectin to possess mitogenic

activity. Many mitogens are "lectins" only if we enlarge the category to include
monovalent molecules with high carbohydrate affinity. Paradoxically, any plant
polysaccharides can be thought of as "reverse lectins" i.e. their sugars bind
lectin-like receptors on the call. This has been demonstrated for polysaccharides
isolated from Thuja occidentales, which show high mitogenic activity that is
blocked by anti-interleukin I antibodies, This proves that plant polysaccharides
are definite biologic response modifiers. Other polysaccharides from higher plants
such asBaptisia tinctoralis (heteroglycans) or Angefica acutiloba ("Angelica
immunostimulating polysaccharide") and the fungii Basidlomycetes (lentinen,
schizophylan, pachymaran and krestins) have also shown mitogenic and respose
modifying activity.

How mitogens work is still imperfectly understood. Con-A has been shown to
induce microtubule assembly in polymorphonuclear leukocytes. Lectins have been
shown to cause early changes in cytoplasmic free Ca2+ and influence the
lymphocyte membrane potential. Both Con-A and PHA were studied as to their
effect on lymphocyte glycosyltransferase activty. The investigators found that
this enzyme, associated with increased transport activity of sialic acids,
galactose and NAG was stimulated by Con-A but not by PHA. Thus the mitogenic
effects of lectins on lymphocytes is not constant.

Lymphocytes in mitosis are almost never found in peripheral blood, but they were
observed frequently in the blood smears of children who has eaten the North
American shrub called pokeweed (Phytolacca amer.) Pokeweed mitogen is one of
the few lectins that stimulates B lymphocytes as well as T lymphocytes. In vitro it
triggers the production of IgE as well as other antibody isotypes. The discovery
that grass pollen apparently share a common lectin perhaps offers a clue as to
why pollen so often provoke allergy.

Lymphoid cells from patients with chronic lymphatic leukemia bind less PHA than
do normal cells, and react poorly to the mitogenic activity of this and other
lectins. B lymphocytes stimulated by lectins are capable of synthesizing
antibodies; T- lymphocytes may be turned into "killer cells" that destroy any
foreign cells that they contact. Many subpopulations of lymphocytes are
specifically stimulated by particular lectins. Separating mouse thymocyte
populations into two groups, one that was agglutinated by peanut lectin and one
that is not. The thymocyte population found to not be agglutinated by the lectin
was found to resemble the adult circulating lymphocytes. Only this population of
thymic lymphocytes has a high sialic acid content on its membrane, leading
researchers to speculate that the attachment of sialic acid to the lymphocyte
surface was a crucial maturation step.
Immunosuppresive effects

Since blastogenesis can also occur in suppressor -T cell populations, it is quite

feasible that significant suppression of graft versus host responses in tissue
transplants can be accomplished by the use of lectins. Significant studies are
now under way at Stanford University showing that lectins can be used
exclusively to maintain transplants in animals for up to two years. Lentil lectin
induces striking transplant tolerance In both mice and humans. Peanut agglutinin
has been used to isolate suppressor T-cells in vivo, these having been first
Induced by Con-A. Tomato lectin has been shown to inhibit the transformation of
peripheral lymphocytes challenged by recall antigens, and actually suppressed
spontaneous DNA synthesis. The inhibition of lymphocyte transformation was not
stopped by exogenously added Interleukin 1 and/or Interleukin 2, even at
extremely high concentrations. This could be significant as the average American
diet results in the ingestion of at least 200 mg. of tomato lectin annually, with
vegetarians probably ingesting a far greater amount.

PHA has been shown to suppress experimental autolmmune thyroiditis in mice for
up to 7 week. Electrolectin from the electric eel (Electrophorus electricus) was
shown to prevent and effectively treat experimental auto-immune myastenia
gravis in rabbits, considered a good model for the human disease myastenia
gravis. Administration of electrolectin to the afflicted rabbits lead in all cases to
complete recovery, presumably through modulation of the suppressor cell activity
directed against acetylcholine receptor protein self antibodies.

Chinese bitter melon lectin (Mornordica charantia) has been shown to possess
potent immunomodulatory activity. "Locoweed" and several species
of Astragalus and Oxytropis, when fed to yearling ewes, resulted in a gradual
decrease in total leukocyte and peripheral lymphocyte blood levels.

Blastogenic effects

The lectin most studied in humans as regards to mitogenic effects is pokeweed

mitogen (PWM), isolated from Phytolacca arriericana.Phytolacca lectin is one of
the rare lectins which is mitogenic for both T and B lymphocytes. Recent studies
on the plant show that salt water extracts of the plant yield five separate lectins,
designated Pa-l through Pa-5. Pa-1 seems to be the only heamagglutinating lectin,
and is powerfully mitogenic. Pa-2 and Pa-4 are the predominant mitogens in the
roots. Pa-1 is mitogenic for both B and T cells, while the other four lectins are only
mitogenic for T cells. Interestingly, PWM blastogenesis is inhibited by other
lectins such as WGA.Benincasa cerifera, used in Sino-chinese medicine as an
antinflamatory diuretic, was shown to contain a powerful anti-tumor mitogen
termed "B. cerifora mitogen" (BCM). Salt water extracts of the seed were shown
to contain B cell mitogenic, adjuvant active and antitumor active substances.

Wheat germ agglutinin (WGA) induces proliferation of T-cell colony forming units
and growth factor production. PHA can induce the acquisition of T cell surface
markers in peripheral blood in the absence of the normal maturation controls of
the thymus. Other studies showed that this occurred only in high IL-1
environments. This was shown to be produced by "mitogen induced erythroid
burst promotion" due to monocyte blastogenesis produced by Con-A. Interestingly
PWM did the exact opposite (suppressed erythroid burst activity), which could
account for the anti-inflamatory activity traditional ascribed to the plant. Human
peripheral blood lymphocytes precultured with lipopolysaccharide from E.Coli
(LPS) were shown to have a greatly enhanced blastogenic response when
pokeweed mitogen was added to the suspension.

Injections of lentil lectin into the knee joint cavity of non-sensitized rabbits
resulted in the development of arthritis which was indistinguishable
morphologically from rheumatoid.

In a rather perverse way "negative-blastogenesis" can also be produced by using

appropriate sugar molecules to "suppress the suppressors". Several sugars have
been shown to selectively do this including mannose and fucose. Lectin Induced
blastogenesis may have some impact In the myeloproliferative disorders. Hodgkin
disease cells have been shown to elaborate an agglutinating lectin on their
surfaces.

Lectins and Malignancy

No other property of lectins has attracted as much attention as their ability to

agglutinate malignant cells. This was discovered by chance at Massachusetts
General Hospital by Joseph C. Aub in 1963. Aub believed that the difference
between cancer cells and normal cells lay on their surfaces; and that alterations
in the properties of the cell surface enabled cancer cells to multiply when normal
cells would not, detach from their primary site and spread throughout the body. At
the time the idea seemed quite strange, and as Nathan Sharon, in his review
article on lectins In Scientific American, put it: "bordered on lunacy".

Aub worked with several enzymes, trying to determine whether the surface of a
malignant cell was different from that of a normal cell. Only in the case of one
enzyme, a lipase from wheat germ, did he observe a difference. Normal cells did
not seem to be affected, but malignant cells were agglutinated. When he replace
the wheat germ lipase with a pancreatic lipase, however no agglutination took
place. Aub also found that the enzyme activity of the wheat germ could be
destroyed by heating, but the agglutination took place all the same. Aub and his
colleagues then discovered that the wheat germ lipase contained as a
contaminant a small protein that was responsible from the agglutinating activity.

Burger and Goldmanberg suggested that the surface of malignantly transformed

cells contained a component which was not found on the surface of normal cells.
It was proposed that this component is NAG or a closely related derivative since
ovomucoid, a glycoprotein rich in NAGs inhibited the agglutination at very low
concentrations. A higher local density of lectin binding sites have been observed
in addition to an interesting phenomenon called "capping" where lectins begin to
cross link more and more surface receptors which result in more and more
binding sites becoming available for cross linking. This eventual tends to cluster
the binding sites to one side of the cell, producing a "cap" which can be observed
by radio identification. This apparently results from a transmembrane effect
involving a glycoprotein, spectrin, which aggregates upon contact with a lectin.
This discovery began a now era in lectin research. Soon it was found that Con-A
also agglutinated malignant cells. Recently the Weizmann Institute of Science in
Israel found that soybean agglutinin also possesses the same property. As a rule
malignant cells are agglutinated by very low concentrations of a particular lectin
and normal cells are not agglutinated unless the concentration is many times
higher. The higher proportion of malignant cells agglutinated probably results
from the sizeable increase in surface receptors on the malignant cells, which
probably results from their incredibly high reproduction rate.

PNA has been shown to inhibit the growth of several breast cancer cell lines, In
addition to allowing for the destruction of breast cancer cell In harvested bone
marrow with a highly effective and selective (3 or 4 log depending on the cell
type) action.

It has been speculated that the production of wheat germ agglutinin protects the
young swelling seed from fungii and other chitin containing organisms. It is
interesting to speculate on the traditional effectiveness of wheat grass
preparations in certain malignancies, in light of the high lectin content within the
seed at the time of preparation. In addition, perhaps it is the heavy use of soy
products found in macrobiotic cookery (and the concurrent high intake of soybean
lectin) which has resulted in the many positive responses to cancer ascribed to
this form of diet.