The “skin” is up on 100 College Street, future home of Alexion Pharmaceuticals — and heartbeats are beginning to race downtown.

Alexion is the first major step in undoing the divide that many blame for the secular destruction of downtown a half-century ago.

What was once called the Oak Street Connector (officially Richard C. Lee Highway) is a 1.1-mile-long freeway section of Route 34 that begins at the junction of I-95 and I-91 and terminates at York Street, the Air Rights parking garage.

The connector and Route 34 itself turned into a downtown divider, renting a neighborhood asunder and placing a highway right through the city center. The connector would eventually undermine the goals of Mayor Richard Lee in rebuilding downtown New Haven.

For decades the state department of transportation wouldn’t give up the dream, or more importantly the property, on Route 34.

The wisdom brought on by a growing city, an aggressive mayor (DeStefano) and an empowered legislative group finally brought the state and its Department of Transportation to heel, allowing the city to create the vision of Downtown Crossing.

The Downtown Crossing project will replace the “limited-access highway stub that cuts through downtown with a pair of urban boulevards” and get pedestrians and cars on street level again.

One Hundred College Street sits next to Yale-New Haven Hospital and the Yale School of Medicine, and also abuts 300 George Street, home to several biotech companies including Achillion Pharmaceuticals. A public company whose stock is on the rise, Achillion itself may soon spread its wings from a pure research company to a full pharmaceutical developer.

The 100 College Street building will be 500,000 square feet, and cost more than $140 million.

Alexion Pharmaceuticals, currently in Cheshire (its present property is on the market), had first committed to occupy 300,000 square feet, but the company later pushed for the project to expand to 500,000 square feet and its own occupancy to 400,000 square feet.

There will be some street-level retail on College Street and the Yale School of Medicine will occupy approximately 100,000 square feet as well.

Alexion currently has a $32 billion market cap,, annual sales in excess of  $1.5 billion and profits of more than $250 million in the past year.

Economic-development officials became nervous, though, when rumors circulated earlier in the year that Alexion was a takeover target by Swiss pharma giant Hoffman Roche.

The idea didn’t go anywhere. The Motley Fool, an investor-oriented media outlet, called the rumor one of the “three most ridiculous” biotech investment ideas of the year. Since then the lift has gotten even harder for a would-be acquirer as Alexion’s market cap increased by 50 percent from $20 billion, making a buyout even more difficult.

It’s not that a pharma giant couldn’t swing the vig: By contrast Pfizer offered $116 billion for Astra Zeneca (which it turned down). But AZ has annual sales of $25 billion and profits of $2.5 billion, making it ten times Alexion’s  size — but only three or four times more expensive.

Alexion is a strong and growing company but it has made its success by developing treatments for rare diseases, not the stuff of “Big Pharma.”