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HeLa Cells, Blue Baby Operation & Restriction Enzymes – Contribution of Baltimore

Exceptional Contribution of Baltimore To Science

Yesterday I happened to visit Baltimore. It’s the 12th largest city in the United States, it was founded in 1729, it has a free bus service called the Charm City Circulator, and it’s 32′C Celsius today (89 Fahrenheit). Excellent. Taken from the coat of arms of the House of Baltimore, the family motto is translated ‘Deeds are masculine, words feminine’. It was misogynist, and I didn’t like it. However, Baltimore is not just the birthplace of David Hasselhoff, Babe Ruth and Michael Phelps. It’s also the home of a lot of brilliant and interesting science. Here are my top three findings today:

1. HeLa cells: Sixty years ago, the cause of one woman’s death was also the beginning of her immortality. Doctors at Johns Hopkins Hospital in Baltimore excised slices of her cervical tumour without her knowledge or consent, and scientists grew her tissues into the world’s first immortal cell line. These cells quickly became one of the most valuable tools in biomedical research, while her family suffered from health problems and debt. Her name was Henrietta Lacks, and her cells are known to us as HeLa. In the early days, HeLa cells were used to test polio vaccines, cancer treatments, and more, and by 2009, over 60,000 scientific articles had been published about research done on HeLa cells. It’s fair to say that scientific research would not be the same without her unknowing contribution.

You can read all about this fascinating story in Rebecca Skloot’s brilliantly researched, somewhat long book called The Immortal Life of Henrietta Lacks.

2. Blue baby operation: In 1944, a paedatric cardiologist Dr. Helen Taussig and surgeon Dr. Alfred Blalock of Johns Hopkins Hospital in Baltimore pioneered the first operation to correct a baby’s blood flow problem. Dr. Taussig hypothesised that blue baby syndrome was caused by leaking between the chambers of the heart, and a constricted pulmonary artery – when this artery functions well, it should take bluish blood without oxygen from the heart to the lungs, to be replenished with oxygen (becoming red). But when it’s tightened, the baby takes on a bluish colour (called cyanosis) and either dies or faces life-long problems. The doctors trialled the operation on hundreds of dogs, before successfully performing it on a baby. We now know that there are many different heart defects, all present at birth, that can cause cyanosis, and there is surgery to improve most of them. This operation pioneered in 1944, called the ”Blalock-Taussig Shunt”, paved the way for open-heart surgery.

3. Discovery of restriction enzymes: Much like we have enzymes in our stomachs to break down food into its smaller particles, bacteria have enzymes that chop up foreign DNA. It’s a kind of immune system, where they can break down invading DNA, like that which a virus would inject into them. Scientists discovered these enzymes in the early 1960s in Baltimore, and found that they were very specific for the sequence of DNA bases that they slice in between. So, for example, an enzyme from the bacteria Serratia marcescens, called Sma1, recognises the DNA sequence CCCGGG, and cleaves it between the C and G, and the same on the opposite (complementary) strand, leaving blunt ends.

An enzyme from E.coli, called EcoR1, cuts the DNA sequence GAATTC between the G and A, if ATTC follow, and this leaves what are called sticky ends, or overhangs. Because the enzyme is restricted to only one cleavage site, it’s called a restriction enzyme.

The three scientists who discovered the enzymes were awarded the 1978 The Nobel Prize in Physiology or Medicine, and two of them worked at Johns Hopkins University in Baltimore.

Why on earth is this interesting to anyone who didn’t work with these enzymes every day of her PhD?

In genetic engineering, restriction enzymes are used to insert new genes into DNA by chopping either side of the gene of interest, and then using the same enzyme to chop the DNA that you want to insert the gene into, and then joining the pieces up (of course, it isn’t this straight forward – you need to ensure that the correct DNA sequence flanks both portions, but you can engineer that too using other enzymes).

Also, these enzymes are used in forensics and paternity tests. If you add a specific enzyme to the DNA you have extracted from someone’s white blood cells, or their cheek cells from a swab, the enzymes cuts the DNA in predictable places, and you can separate these pieces by their size. What results is a very distinctive pattern, a genetic fingerprint. In the picture on the left, you can see the DNA fingerprint of a father (1), child (2), and mother (3). And since the child inherits its DNA from both its parents, each fragment of DNA in the child’s lane corresponds with one in either parent. This confirms paternity in this case (and maternity, but that’s not normally in doubt!). The same technique is used to nail criminals to a crime scene. If their pattern matches the pattern of DNA taken from the scene, then their involvement is proved by looking at how likely it is that a match occurred by chance. This probability could be anything from one in a few thousand to one in many millions. Guilty!

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