Keto Info Week 7/25

[spEEdfrEEk]

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..

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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: