Hamlet

Hamlet

Having dealt with Viagra and the role of NO, nitric oxide, in

enhancing the male”s sexual prowess, I feel obligated to discuss a

female-oriented subject. An obvious subject is the female breast.

Indeed, Brian Trumbore in his weekly review recently attempted

to correlate the financial market”s ups and downs with the

fluctuating bust measurements of someone named Pamela Lee

Anderson. I occasionally do my morning 3-mile walk at a local

mall and cannot help noting, as a scientist of course, larger-than-

life photos in the windows of Victoria”s Secret extolling the

enhanced presentation of a woman”s breasts by the engineering

design of the Wonderbra or its equivalent. In fairness, I should

point out that the male also has breasts. Indeed, a Seinfeld

aficionado will recall an episode in which George was upset that

his father, played by Jerry Stiller, had developed pronounced

breasts in his advancing years. This moved Kramer to invent the

“bro”, counterpart to the more widely known “bra”. To my

knowledge, the “bro” has not been a commercial success. On the

other hand, the Nike sports bra for women received an inordinate

amount of attention recently, thanks to Brandy Chastain”s

removal of her shirt. I don”t understand the media”s interest in

this happening inasmuch as I see many women jogging or

running in our area in their sports bras and no shirts. (OK, I do

understand that in between major tragedies the media does have

to fill their spaces and time with something.)

To keep you up to date on bras, I saw in the weekly Circuits

section of the New York Times that an industrial engineering

design student in London has invented a new “Techno Bra”.

This new bra incorporates a heart monitor, wireless telephone

and Global Positioning System locator! The Techno Bra can

detect a sudden increase in heart rate, call the police and give the

wearer”s location. A stop button is included, presumably to

prevent false alarms, so prevalent in cars these days. The

designer of this security bra is a woman who felt that a feminine

touch was needed since many designers are men, whose designs

are more aimed at men than women. Will the Techno Bra fare

better than the “bro” in the marketplace?

For Dow Corning, the breast is not a subject for humor. Its

contribution to the silicone implants to enhance or perhaps

replace women”s breasts has meant bankruptcy. Only within the

past month does it look like the company will finally get

approval for a reorganization plan which takes into account the

liability, potential or actual, resulting from lawsuits filed on

behalf of over half a million women. These women claim to

have suffered from various complications and diseases resulting

from their breast implants. In fact, a number of scientific studies

have concluded there is no evidence that implanted woman have

any more problems of the types claimed than do women without

implants. Nevertheless, the court cases will probably drag on for

years and years. (Leakage from ruptured silicone implants is

acknowledged to be a problem in some cases.)

Because of the media”s obsession with breast cancer and with the

sensual aspects of the female breast, the primary function of this

organ tends to get short shrift. For many years the benefits of

breast-feeding versus formula feeding of infants have been well

known. The passage to the baby of various components of

mother”s milk enhances the baby”s immune system and the

infant”s development. I saw an article last week reporting that

formula babies were something like five times more likely to be

overweight by the age of 5 than those who were breast-fed. It is

clear that the biochemistry of mother”s milk remains a fertile

ground for exploration.

Of course, a prime concern of any woman these days is the

possibility of breast cancer. The incidence of breast cancer,

according to some studies, varies widely for different

geographical areas and is especially high in the northeastern

United States, with its large industrial base. A small study in

Ontario reported last December found for the first time certain

aromatic amines in human breast milk. Although only present in

parts per billion, these compounds, used in many industrial

processes, are known to cause cancer in rat”s mammary glands.

The authors emphasize that their work should not discourage

breast-feeding because of the great benefits to the infants

regardless of the trace contaminants. They plan to expand their

studies to other regions.

One reads almost daily of some promising new drug or treatment

that hopefully will lead to a cure for cancer but so often these

hopes turn out to be unfounded. However, I was intrigued by an

article by Peter Radetsky in the June issue of Discover magazine.

The article describes very exciting work of Catharina Svanborg

and associates at Lund University in Sweden. If this work pans

out, it could well be that a potent cancer killer might be hiding in,

of all places, the woman”s breast itself, i.e., in mother”s milk!

To understand cancer, researchers have found that a key player is

APOPTOSIS. Apoptosis is a form of programmed cell death;

that is, our healthy cells are programmed to commit suicide when

they receive the appropriate signal. Apoptosis under normal

conditions means that the cells tear themselves apart in a manner

that the leakage of their contents is minimized. Otherwise,

undesirable consequences may result. A key feature of cancer is

that the cancer cells don”t commit suicide, as they should, in spite

of being instructed to do so. Therefore, they keep growing and

multiplying to form tumors in the case of most cancers. Many

years of research have gone into identifying the proteins involved

in the sensing and regulation of apoptosis.

Back to Catharina Svanborg. Her Lund University website states

that her project goals include characterizing the apoptosis-

inducing molecules in human milk and evaluating the anti-tumor

effect in tumor bearing mice. How did this project come about?

According to the Discover article, Svanborg and her group had

been studying mother”s milk and its interactions with the cells

lining the gut of nursing infants. They found that mother”s milk

did a good job of blocking pneumococcus bacteria infection.

They also noted that breast-fed children had fewer ear and upper

respiratory infections. Other studies had shown that the risk of

childhood lymphoma is 9 times greater for those children who

had been formula-fed as compared to those who were breast-fed.

About 7 years ago, Svanborg”s student, Anders Hakansson told

Svanborg that something strange was happening. He had been

mixing cancer cells, bacteria and mother”s milk and found that

the volume of cancer cells was decreasing. Svanborg peered

through the microscope and deduced immediately that the cells

were committing suicide, apoptosis. If the finding had taken

place in a pharmaceutical company, a team of researchers would

have been placed on the project but Svanborg”s group numbered

less than 20. Everyone was engaged in studies on fighting

infectious diseases so it was left primarily to Svanborg and

Hakansson to continue the study. By late 1995, they had

identified the cancer cell killer as an abundant protein in breast

milk called alpha-lactalbumin, or alpha-lac for short. Alpha-lac

had been studied before and was known to help produce lactose,

the sugar found in milk, and nourish babies.

A hot topic in biochemistry these days is PROTEIN FOLDING.

It seems that proteins don”t hang around and do their jobs in

straight chains or linear molecules like you see in simple models

of DNA, with its entwined double helix. Rather the proteins will

fold up in all kinds of shapes and forms. The prion is an example

of a protein, whose function is not known, that apparently sits

around in the brain all folded up and happy. Unfold that prion,

however, and you get mad-cow disease! Svanborg and her

colleagues have come to the conclusion that the alpha-lac also

changes shape, sort of like Clark Kent changing into his

Superman cape. In its folded form it carries on its lactose bit but,

when partially unfolded, it”s transformed into a cancer fighter.

As often happens, serendipity came into play in this project.

When Svanborg prepared the milk to pour over cells, she added

acid to the solution. Well, it turns out that the acid unfolds the

alpha-lac. Actually, Svanborg”s group has found that another

“secret” ingredient in the mother”s milk also has to be present to

unfold the protein. Being Scandinavian, they”ve named the

unfolded alpha-lac HAMLET (Human Alpha-lactalbumin Made

LEthal to Tumor cells).

It turns out that the breast-fed infant”s stomach is at about the

same acid level as the experimental solution and Svanborg

postulates that the folded alpha-lac is unfolded in the stomach to

form HAMLET. HAMLET, now in its crime-fighting role,

searches out suspicious looking cells and persuades them to

commit suicide. Of course, growth is rapid in an infant and cells

are multiplying rapidly. It seems reasonable that in the vast

number of new cells there could be quite a few cells that didn”t

duplicate precisely the normal genetic code. These abnormal

cells, if not destroyed, could be latent cancer cells or cancer

promoters that might be activated years later. If Svanborg”s

scenario is correct, HAMLET and the secret ingredient could

emerge as the Supermen or, more appropriately, Superwomen of

cancer killers. Svanborg”s group has found that HAMLET kills

every form of cancer cell they”ve tested so far and the hope is for

beginning experimental trials in humans by next year. IF these

trials are successful, and it certainly is a big if, the 21st century

could be the century of HAMLET and the conquest of cancer.

Svanborg is just as excited about the possibility that alpha-lac

may be used to prevent bacterial infection, e.g., in hospitals.

Let”s all hope she”s right!

Allen F. Bortrum