CATEGORY: biology/cardiovascular_system
TECHNICAL: **
SUMMARY:
This document duscusses something caled "blood type
conversion". This is a process where blood types A & B (and
in the future AB) are converted into the mother blood type
O. Many of you remember the discussion we had last year about
the blood types and how they evolved. For those who were not
on the list at that point, I'll provide a brief discussion of
it here.
At one point in the human evolutionary record, there
was only one type of human blood. Type O. At some point (recently)
in the genetic history of humans, 3 new "mutated" types appeared.
These are type A, B, and AB. About a year ago, I did some
research into what the cause of these mutations were. Mother
nature doesn't make such a drastic change in evolution, unless
there is a VERY significant change in the human condition. What
I found was this: In essence, blood type A came about due to
the shift of the human diet from hunter-gatherer to more a
more *grain based* diet. As a result, type-A people can usually
tolerate having grain in their diet better than most type-O
individuals. (although this capacity diminishes with age..)
Type B blood evolved in cultures that tended to consume
more dairy. IE: people who had milk and cheese as a staple
of their diets tended to produce later generations with B type
blood. This document sort of clarifies that point by indicating
galactose as one of the sugars that needs to be "clipped" from
B blood. Galactose is a monosaccharide (simple sugar) found
in dairy. Type AB blood is usually found in cultures with
the longest exposure to both grain and dairy (which is a
maximum of 20,000 years.. only a fraction of the human evolutionary
period)
Is it any wonder why I encourage people to stay
away from grain and dairy? Those two, non-natural non-human,
foods were behind what could be considered as a major shift
in the evolution of human blood.
Niether grain nor dairy is a good choice in a healthy
human diet. As I have indicated before, no matter what blood
type you are, the effects of these two foods on your body will
end up harming you in the end. Not only are they the most
allergenic substances known, but they are also the two most
associated causes of cardio-vascular disease, diabetes, MS,
and the rest of the degenerative diseases.. Once again, I
emplore you: Eat like a caveman..

-------------------------------------------------------------

SCIENCE NEWS ONLINE

January 11, 1997

Banking on Blood Conversion

New technology may change the character of the U.S. blood supply

By CORINNA WU

Eager donors arrive at a local blood drive, ready to give the gift of
life. But before their blood is allowed to flow into a plastic bag through
needles plunged into their forearms, they must sit down with a pen and
take a test.

The questionnaire--along with biochemical tests on the blood
itself--is part of a rigorous screening process that has made the U.S.
blood supply one of the safest in the world. As a result of this
vigilance, the risks of contracting AIDS or other infectious diseases from
a blood transfusion have dropped substantially.

Once that blood reaches the hospital, however, even the most careful
initial screening efforts can't protect a patient from getting a fatal
transfusion of the wrong blood type--a situation that occurs more often
than most people think, says Harvey Klein, who is chief of transfusion
medicine at the National Institutes of Health in Bethesda, Md. Sometimes,
amid the chaos of an emergency room, or even in less hectic settings, a
health care worker misreads a label or a chart and gives the wrong blood
to a patient. If blood of type A or B is given to someone with type O
blood, for example, the ensuing severe immune reaction can rapidly kill
the person.

Improving blood-handling procedures and worker training can forestall
such deadly accidents. Some researchers, however, think they may have
found a more foolproof solution by chemically converting types A and B red
blood cells to the universal type O. That way, any unit of blood cells
could be transfused into any patient, removing the need to match blood
types.

This innovation would have the added benefits of correcting
imbalances in blood type inventories, reducing the amount of blood that
gets outdated before it can be used, and cutting the costs of blood
distribution. More than 15 years of research into this technique is
reaching fruition; hospitals and blood centers may have blood conversion
technology by next year.

In any year, as many as 1 in 12,000 units of red blood cells meant
for one person is mistakenly given to another, says Klein, but "most of
the time, that won't cause any harm, just by luck." Type O blood can be
given to anyone, and type A blood presents no problems for someone who
happens to be A or AB.

The real danger arises when, for example, a type O patient gets A or
B blood or when a type A patient gets B blood. Unfamiliar molecules on the
surface of the foreign blood cells trigger the immune system, which kicks
into high gear and throws the patient into shock. The kidneys fail, and
the depletion of blood-clotting factors causes bleeding "from the nose,
ears--every orifice of the body," says Mark Popovsky, chief executive
officer of the New England Region American Red Cross.

About 1 in 100,000 people who receive a transfusion dies, including
most people who get incompatible blood, Klein says. Although the risk of
getting the wrong blood type is fairly low, it spells almost certain death
when it happens. "It's sort of like a plane crash. One in 12,000, I've
always thought, is a frightening statistic," he adds. Moreover, hospitals
may underreport the problem.

Some hospitals try to lessen the chance that a hurried doctor or
nurse will make a fatal mistake by stocking only type O blood for
emergency rooms and intensive care units, Klein says. This practice,
however, can create a shortage of type O blood for the region.

On the other hand, between 5 and 10 percent of A and B blood goes to
waste, says Popovsky, simply because hospitals can't use those units
within their 42-day shelf life.

To minimize the waste of usable blood, hospitals sometimes ship their
surplus to other institutions in the region that need more than they
anticipated. Blood also travels between neighboring regional blood
centers.

"No one has good data on how frequently blood is moved around," Klein
says, but "we know that there is a lot of movement."

Conversion of all blood to type O can address these supply imbalances
and reduce the amount of shipping necessary, says Jack Goldstein of the
Kimball Research Institute at the New York Blood Center, who is one of the
pioneers in the field.

The idea explored by Goldstein and other researchers is to use an
enzyme to alter the chemistry of the red cell surface. Chains of sugars,
which cover the cell surfaces of the four human blood types--A, B, AB, and
O--all have the same basic sequence, with fructose at the end and galactose
next in line.

The major distinction between types lies with the sugar that branches
off from the galactose. On A cells, that sugar is N-acetylgalactosamine.
On B cells, it's another galactose. O cells have no additional sugar at
all, while AB blood cells bear a mix of A and B chains. In the United
States, about 45 percent of the population has type O blood, 40 percent
has type A, 11 percent has type B, and 4 percent has type AB.

A and B cells cannot be transfused into people with O blood because
the extra sugar branch stimulates the immune system's antibodies to attack
the foreign cells. Clipping off that additional sugar branch from A and B
cells transforms them into type O, averting the immune response.

Goldstein found the right enzymes for the job in what might seem to
be some unlikely places. He isolated the enzyme for B conversion,
a-galactosidase, from coffee beans. "It's not so far-fetched," he says.
Beans and seeds use the enzyme to break down large molecules into
individual sugars, which provide energy.

The enzyme for A conversion, a-N-acetylgalactosaminidase, came from
chicken livers. These digestive enzymes, Goldstein says, are "ubiquitous
in nature, but you have to use the right ones." In the beginning, he
needed 50-pound batches of both coffee beans and chicken livers to get the
necessary quantities of enzyme for experiments. "I think Mr. Perdue [the
chicken magnate] was happy for a few years," Goldstein says. "We used a
lot of chicken livers. [It was] so traumatic, I put them out of my mind."

Researchers don't need to wallow in vats of chicken innards or mounds
of coffee beans anymore. With the techniques of biotechnology, the enzymes
have been cloned and are now synthesized in bulk.

The large number of sugar chains and their different orientations on
cell surfaces made finding the right conditions for conversion a real
challenge, says Goldstein. Type B cells have over half a million sugar
chains on their surface, while type A cells have twice that amount. Some
are perpendicular to the surface; others lie parallel.

"This is what fascinated me," says Goldstein, "to get enzymes and
conditions where the enzymes would work." For example, the enzyme for B
conversion works best at a high acidity, but blood cells do their job of
carrying oxygen in neutral conditions. Goldstein had to strike a balance
that allowed the enzyme to efficiently clip off the extra galactose
without destroying the red cell's function. Eventually, he determined that
the reaction could take place at 26oC, rather than the higher temperature
the blood cells are accustomed to, and at a slightly acidic pH of 5.5 or
5.6.

"When I started this work, no one had really treated red cells at
such a low pH," he says. "It was thought that they would just become
nonviable." That turned out not to be the case. Not every sugar chain on
every cell gets changed, he says, but as long as enough are clipped, the
body accepts the cells.

A company called ZymeQuest in North Andover, Mass., is currently
conducting clinical trials to determine whether converted B cells have the
same medical utility as unconverted O cells. So far, studies have shown
that converted B cells behave like normal O cells and don't trigger any
immune reaction.

ZymeQuest, which holds the license to develop Goldstein's technology,
has designed an automated machine that performs the B-to-O conversion.
Able to convert many units of blood with little human intervention, such
machines could easily be incorporated into the daily routine of regional
blood centers, says president Douglas Clibourn. He estimates that the
company should have a salable product by the end of 1998, pending approval
by the Food and Drug Administration.

A similar technique could be used for A-to-O conversion, but that
project is about a year behind. Effectively converting A cells is trickier
than altering B cells, because about 75 percent of people with type A
blood have two kinds of sugar chains on their cells. Out of the million or
so structures on each A cell, about 50,000 have a second copy of the final
three-sugar sequence, which includes an N-acetylgalactosamine. "It's not
that far in, but it means that one has to use a different approach to
remove it," Goldstein says. "We're very close to solving this problem."

Starting experiments with type B blood turned out to be a good
choice, he says. "If we had started with A, maybe I would have dropped
this project earlier."

Once conversion technology for A and B blood is established, altering
the AB cells should be straightforward. "The cost of converting all the A,
B, and AB blood to O," Clibourn says, "is less than the current cost of
all of that blood shipping."

Any technology that would convert blood to a true universal donor
type must take another characteristic, Rh factor, into account. A cell
surface protein first discovered in the blood of Rhesus monkeys, the Rh
factor can provoke an immune reaction in people whose blood doesn't
normally carry it. People who have the protein on their red blood cells
are deemed Rh-positive; those who don't are Rh-negative.

Rh incompatibility is less of a problem than ABO incompatibility,
says Klein. A majority of people in the United States, about 84 percent,
have Rh-positive blood.

Moreover, an Rh-negative person can withstand one accidental
transfusion of Rh-positive blood because the Rh-negative person doesn't
develop anti-Rh antibodies until 3 or 4 months later, Klein says. "The
second transfusion, after they already have that antibody they made as a
result of the first transfusion, could be very serious." An Rh-negative
woman who develops antibodies from bearing an Rh-positive child faces that
risk if she conceives a second Rh-positive child or receives an
Rh-positive blood transfusion.

Several labs have cloned the Rh factor, Goldstein says, but no one
fully understands its three-dimensional structure. Therefore, researchers
are only beginning to explore techniques for Rh conversion. If researchers
can identify which part of the protein stimulates the immune response,
then perhaps they can alter that portion to make the blood cell
effectively Rh-negative. Eventually they want to produce type O,
Rh-negative blood--the kind any person can receive without fear.

Despite the promise this technology holds, it doesn't produce a
limitless supply of blood, Popovsky says. The key factor in maintaining
the blood supply is still sufficient donation.

"Today, the demand for blood is very great," Popovsky says. "We need
healthy people to donate so that they support the blood system of this
country. Without them, it would collapse." Although there is talk about
artificial blood substitutes, he adds, humans still cannot chemically
synthesize molecules that can do everything a red blood cell does. "The
human red cell is a fantastic structure--there's nothing like it."

copyright 1997 Science Service

:cool: TJ :cool: