Reality check: Could MH370 have hidden from radar next to another plane?

Published on GlobalPost

Yes, says an MIT aeronautics professor. With caveats.

BOSTON — It’s the Malaysia Airlines missing jet theory that has taken the internet by storm.

Ohio aviation hobbyist and IT professional Keith Ledgerwood dug deep into the data and emerged with the idea that — after making the sharp left everyone seems to now agree on — flight MH370 appears to have piggybacked on another aircraft, Singapore Airlines Flight 68, which also departed Kuala Lumpur around the same time.

In doing so, the theory goes, it could have evaded radar detection. Unlike MH370, which was heading for Beijing, SIA68’s destination was Madrid. Its flight path passed over parts of India, Pakistan, and Afghanistan, after which the Malaysian Boeing 777 could have peeled off and landed in the desert or in Central Asia.

The hypothesis, replete with charts and technical details, is compelling. But is it feasible?

Yes it is, according to Massachusetts Institute of Technology professor of aeronautics and astronautics R. John Hansman Jr.

But it’s not very likely.

An airplane as big as a Boeing 777 can effectively hide from radar systems, Hansman says, if it gets close enough to another plane of similar size. Hansman is also the director of MIT’s International Center for Air Transportation.

Speaking to GlobalPost Tuesday, he said he was familiar with Ledgerwood’s idea, and termed it “technically possible but operationally very difficult.”

Hansman said with planes of that size, “you don’t have to get that close — within a half-mile or a quarter-mile” to appear on radar screens as, effectively, part of the same plane, even on military radar.

“It would be a slightly larger radar blip, but not enough to get anybody’s attention,” Hansman said. Since radar operators would be expecting to see a contact at that speed and on that flight path — they would be assuming it was only SIA68 — they would not see anything worrying.

However, maneuvering two massive aircraft that close together in flight at high altitude is extremely hard, he said.

More from GlobalPost: How do you make a Boeing 777 full of passengers vanish?

First, while the flights departed from the same airport, “it’s hard to catch up with the other airplane.” Big airliners don’t have much of a range of possible speeds, especially when flying at cruising altitudes, so it’s not like the Malaysia Airlines pilot could have done the airplane equivalent of stepping on the gas pedal — it would have already been quite near the floor.

If it was possible to catch up with speed, the Malaysian pilots would have had a challenge locating the Singapore Airlines plane — having turned off their transponder and anti-collision signaling systems, that equipment would have been useless to provide other planes’ whereabouts.

Transponder silence also would have prevented the Singapore Airlines plane from noticing it had a shadower, Hansman said, as airplanes’ on-board primary radar is designed to detect weather, not other aircraft.

Even assuming MH370 could catch up to, find, close in with, and shadow SIA68 in the middle of the night over the ocean, “at some point you’re going to have to separate” and fly elsewhere, Hansman said. “Then you have to land it somewhere.”

As suggested by another aviation expert speaking to GlobalPost, being certain of escaping radar detection all the way to landing at a remote airstrip would mean discovering and evading secret military radar capabilities, or at least being absolutely sure that the nations in question would not want to expose their technological expertise by sharing information those systems might have detected.

Hansman discounts the possibility of a thief having run off with the plane because “it’s easier to just go out on the ramp and steal an airplane” than to gain enough expertise to accomplish what Ledgerwood’s hypothesis suggests, and then to go and actually execute it.

He is more persuaded by an idea he and others have been discussing for several days: The possibility of some sort of onboard emergency, an electrical malfunction or a fire, like that described in a Wired post earlier Tuesday.

“The original turnback” — the one Ledgerwood thinks was to chase SIA68 — “was in a direction toward an appropriate emergency-diversion field,” Hansman said.

But even that change raises questions for him: In an emergency, pilots wouldn’t likely have taken the time to use the flight computer, but would instead have changed the plane’s heading manually. And if there was time to use the computer, he said, there would have probably been time to make a radio call announcing the problem.

But Hansman said the basic assumption of Ledgerwood’s idea is true: Only very high-tech radars can tell the difference between two planes traveling close together at altitude, and many countries in South Asia may not have that equipment. In fact, “we hope not,” Hansman said.

Five Prime steps up search for monoclonal antibodies

Published in Drug Discovery News

SOUTH SAN FRANCISCO, Calif.—Seeking to continue, and accelerate, its work developing new protein therapeutics for cancer and inflammatory diseases, Five Prime Therapeuticshas made an agreement with Adimab of Lebanon, N.H., that will help discover monoclonal antibodies for cancer immunotherapy. Five Prime also recently closed its initial public offering, raising $43 million.

 

Under the terms of the Adimab deal, which marks the first time the companies have worked together, Five Prime will identify potential targets for development as therapeutic candidates and send them to Adimab for discovering and optimizing the corresponding fully human antibodies.

 

Five Prime will then develop and commercialize those antibodies, with Adimab receiving not only payment for each target campaign, but also potential milestone payments and royalties, according to a news release from the company. Specific financial details were not disclosed.

 

“Working with Adimab, we will be generating antibody products to targets of our choosing, and these could become clinical candidates for Five Prime’s proprietary pipeline,” Five Prime Chief Business Officer Aron Knickerbocker told DDNews in an email.

 

Five Prime has “a library of over 5,700 extracellular proteins (ligands and receptors),” Knickerbocker wrote. “We believe these include substantially all medically important protein drug targets, including many proteins not in public domain.”

 

Five Prime can produce “thousands of proteins weekly,” from which it screens “novel protein therapeutics and antibody targets,” Knickerbocker wrote.

 

From there, Adimab will use its library of fully human whole immunoglobulin-G molecules (IgCs), and its technology that rapidly identifies appropriate matches, returning results to Five Prime. While Knickerbocker declined to talk about project timelines, Adimab’s website says its usual turnaround from target receipt to return of purified, whole IgGs is eight weeks.

 

That includes screening more than 10 billion IgGs from its various libraries; past results have “generated large numbers of fully human IgGs (100s up to 1000s) to all targets screened to date,” Adimab’s website says.

 

“Working with Adimab will allow us to generate fully human monoclonal antibodies to our targets of interest,” said Knickerbocker.

 

The advantages of being able to test with full antibodies are significant. Unlike the more commonly used antigen fragments, whole IgGs are capable of cross-linking receptors, as well as sterically blocking interactions.

 

Less than a month after announcing that agreement, and highlighting its progressing collaboration with British pharma giant GlaxoSmithKline developing FP-1039 (GSK3052230), a fibroblast growth factor ligand trap targeting multiple solid tumors, Five Prime also grossed $43,125,000 in its initial public offering of 3.4 million shares of common stock. The company trades on the NASDAQ exchange, with symbol FPRX.

We have a problem: The science behind rising seas

Published on GlobalPost

A hundred years after it spawned the iceberg that sank the Titanic in the North Atlantic, the Jakobshavn Glacier is now a major contributor to global sea-level rise, this time threatening the homes and lives not of 2,200 passengers and crew but of a billion people across the world.

As climate-watchers and coastal-dwellers keep a weather eye out for signals of irreversible changes in the environment, the world’s fastest-moving glacier has already begun self-destruction. 

Jakobshavn is now shedding ice nearly three times as quickly as it was 20 years ago, dumping enormous and growing quantities into the ocean. It's contributed 0.1 millimeters per year to worldwide sea-level rise — more than 3 percent of the 3 mm produced globally — for the past decade.

The glacier “has been retreating for the last 100 years,” according to Ian Joughin, senior principal engineer at the Polar Science Center, part of the University of Washington's Applied Physics Laboratory. “Retreat” means a glacier is shrinking in length, losing more ice from its face that meets the water than accumulates from higher up.

But it was only in recent decades that the retreat reached extreme levels.

Jakobshavn’s story isn’t unique. For decades now, more ice has been melting into the ocean than is falling from the sky in the world’s mountain and polar regions, where ice sheets store two-thirds of the planet’s fresh water — and the science shows us the situation won’t reverse any time soon.

To understand exactly what’s happened and what's likely to come, it’s critical to understand the topography underneath each glacier.

First, a note on how to think about glacial ice: it's not as simple as frozen water. Scientists consider glaciers to be "nonlinear viscous fluids," which behave like both solids and liquids. Think of a glacier as a frozen river, always flowing at some speed from source to outlet, but growing and receding with the seasons. Because ice is heavy and not a perfect solid like rock, it flows under gravitational pull and pressure from above. Sometimes big chunks become unstable and fall into the sea. When Earth’s climate is in balance, about the same amount of water flows into the oceans from glaciers as is evaporated and then precipitated as snow onto ice sheets from which those glaciers are made.

The Jakobshavn Glacier, known in Danish as Jakobshavn Isbræ, has its origins in large areas of land well above sea level, from which it flows down toward the ocean (in this case, Ilulissat Icefjord), where it calves icebergs into the water.

As physicist Joughin describes it, Jakobshavn Glacier flows off the land and into the 1,600-meter-deep fjord, filling it entirely with ice for a distance of about 50 kilometers, ultimately climbing up a slope in the sea floor that peaks at about 600 meters of depth. The narrow sheet of ice coming off the edge of the glacier at that peak — called a “glacier tongue” — once served as a sort of “cork” for the glacier, holding it back significantly and preventing quicker loss of ice.

You can see the rise in sea-bed elevation just to the left of center in this graphic.

In 1992, Jakobshavn was melting at a rate of about 6 kilometers a year. It was “about in balance” with the natural rhythm — gaining and losing roughly the same amount of ice over the course of a year’s winter accumulation and summer melting, Joughin said.

But in the late 1990s, the glacier’s tongue broke off, and the “uncorked” Jakobshavn began to calve and lose mass in ever-deeper water.

By 2000, the glacier was losing 11 kilometers in length every year, nearly twice the stable speed. As of last summer, according to a paper Joughin and others published recently in academic journal The Cryosphere, it was losing nearly 17 kilometers a year, retreating up the fjord into increasingly deep water that could cause it to melt even faster in the coming decades.

Jakobshavn’s dramatic change was recorded in the 2012 film "Chasing Ice," in a compelling scene that captured the calving of a kilometer of ice in a single event. That happens throughout the summer, Joughin said, though not always in such significant individual moments. (When it does, though, global seismic monitors have been known to register them as 4 or 5 on the Richter scale, he said.)

Eventually — perhaps in about 100 years — the glacier will have retreated far enough that it will no longer feed directly into the fjord. At that point, essentially landlocked, the glacier will only shrink through melting, which happens much slower than calving. With that slowing will come more stability in terms of the glacier’s size. “The next stable condition could be a regionally smaller ice sheet,” Joughin said.

Jakobshavn would still contribute a significant amount of global sea-level rise before then. But the real danger lies at the other end of the Earth, in the West Antarctic Ice Sheet (WAIS), which holds enough water to raise the ocean between three and six meters.

The WAIS is also melting, but it’s doing it in open water; once the process starts, the sheet will never stop calving.

“The [WAIS] glaciers are going to keep retreating. At this point there is nothing we can do but watch,” said Eric Rignot, a glaciologist at the University of California Irvine who published his latest paper about the WAIS in December’s Geophysical Research Letters. “Just how fast they can flow, we don’t know,” he said.

It could take hundreds or thousands of years, but as Joughin puts it, the next stable point for WAIS is “no ice sheet.” By then huge areas of land, home to massive proportions of the world’s population, would be under water.

The question facing scientists and coastal dwellers is akin to the one facing the Titanic’s passengers: The water is rising, and we don’t quite know how fast it’s coming, or how quickly it will accelerate. But we need to plan, move, and adapt if we are to survive. There’s no way to stop the water, and no time to waste.

GSK, Roche go head-to-head to fight melanoma

Published in Drug Discovery News

LONDON—Taking a lead in the tight race to develop and release melanoma medications,GlaxoSmithKline plc (GSK) has received accelerated approval from the U.S. Food and Drug Administration for its combination of Mekinist (trametinib) and Tafinlar (dabrafenib) for treatment of melanoma with BRAF mutations V600E and V600K. Roche, which is also a big player in this market, is now behind, said Aine Slowey, senior analyst for London-based analysis firm Datamonitor Healthcare. While both GSK drugs had been approved as monotherapies in 2013, the combined results “were very positive and significantly better than the BRAF monotherapy,” Slowey said.

 

The Swiss giant has a monotherapy in Zelboraf (vemurafenib) but does not yet have a combination therapy targeting BRAF mutations. In fact, “the combination of  Zelboraf and Yervoy has already crashed and burned,” she said. While Zelboraf is less toxic than Bristol-Myers Squibb’s (BMS) Yervoy (ipilimumab) and therefore may be used first, with Yervoy going only to those who see no improvement, a combination of the two drugs was hoped to be a powerful one-two punch. But the trial combining them was halted last year because of toxicity.

 

In the wake of that failure, Roche may be looking to “leapfrog” GSK, to combine dual therapy with additional PD-1 inhibitors, she said.

 

Both GSK’s approved dual treatment and the failed combination from Roche and BMS inhibit MEK as well as BRAF, delaying medication resistance that arose when inhibiting just BRAF. But it’s only a delay, Slowey said; eventually resistance does develop. Adding immunotherapy, such as PD-1 inhibition, may help, Slowey said.

 

Melanoma medications are a small, and relatively new, market. The disease is easily detected in its early stages, and surgery is usually both quick and effective, particularly when compared to surgery for other types of cancer. But basic research uncovered the fact that BRAF mutations are a “convenient biomarker that patients are going to respond well to this kind of targeted therapy,” Slowey said, so companies started exploring commercialization.

 

For those patients who do develop metastatic melanoma, about half have a BRAF V600 mutation; of those, 90 percent have the V600E variant, Slowey said. (The other half, who have what is called “wild-type” metastatic melanoma, get Yervoy and immunotherapy, Slowey said.)

 

While Datamonitor projects patient numbers will grow about 3.5 percent a year through 2021, the market numbers are still low: Seven years from now, there will only be 170,000 patients in the U.S., Japanese and European markets combined, the company projects, with sales totaling $459 million then.

 

Nevertheless, “it’s probably one of the fastest-moving oncology markets at the minute,” Slowey said.

 

Prior to 2011, only standard cytotoxic chemotherapies were available. But then Yervoy was approved for metastatic melanoma patients. Already there are four approved drugs, with more on the way.

 

BMS has entered the fray, winning fast-track designation for nivolumab, which is now in Phase 1 trials, as well as combination testing.

 

And Merck’s PD-1 inhibitor, MK3754, has breakthrough designation for treating melanoma; the company recently signed a deal with Amgen to see if MK3754 would work well in combination with Amgen’s oncolytic virus Talimogene laherparepvec.

Growing proteins in space

Published in Drug Discovery News

BOSTON—Taking protein-growing to high altitude and low gravity, Emerald Bio has joined an arrangement led by the Center for the Advancement of Science in Space (CASIS) and catalyzed by the Broad Institute of MIT and Harvard to send labs on chips to the International Space Station to study growth of proteins that may help develop treatments for cholesterol and cancer back here on Earth.

 

Though Melbourne, Fla.-based CASIS has offices in Cambridge, Mass., this is the first time the NASA-selected manager of the International Space Station U.S. National Laboratory has collaborated with the Cambridge-based Broad, according to Brian Hubbard, director of the Broad’s Therapeutics Project Group.

 

The Broad does work frequently with Emerald Bio, though, and when Hubbard heard last summer that CASIS was interested in growing proteins in space (which had been done before, but not with current technology), he thought of Emerald. “It came together very quickly,” Hubbard tells DDNews, crediting the Broad’s “open collaborative model” with the efficiency. “You don’t need to form a team. The team is already there.”

 

And it’s a diverse but focused team. In addition to CASIS, Emerald and the Broad, the crew also has NanoRacks of Houston (which has scientific hardware on the ISS) and Protein BioSolutions of Gaithersburg, Md., which recently purchased from Emerald the microfluidic technology that will enable more than 7,000 separate protein-growth experiments to fit in the space allotted on the space station.

 

“We were actually approached by CASIS … through the Broad,” George Abe, president of Emerald Bio, says. With available time and energy, CASIS was interested in new reasons for growing proteins in microgravity. And CASIS wanted something of real therapeutic value.

 

Emerald suggested two possibilities: proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene that raises LDL (low-density lipoprotein) cholesterol, and myeloid leukemia cell differentiation protein 1 (MCL1), a key gene in cancer treatments.

 

Neither structure has “been solved in its empty state before,” Abe said. Protein structures are “extremely sensitive to a lot of environmental factors,” Abe said. “A protein structure will grow or evolve differently in a microgravity environment than on planet Earth.” How they grow when freed from Earth’s gravity could provide new information that will lead to approaches to inhibit relevant genes.

 

That direct approach is typical of the Broad, Hubbard said. “We’re looking to have real impact on patients but we’re also looking to . . . disruptive technologies” with prospects not today but five to 10 years out, he said. Often, if things aren’t druggable directly, researchers work to find the relevant genes, then proteins and then follow the thread back through gene regulators, eventually finding something that is druggable, he said. But at the Broad, they go for the target itself, even if that means inventing new technology, Hubbard said.

 

And while the technology itself already existed, the method had to be created to allow this research to proceed. Originally, Emerald had thought it might send the equipment to grow proteins up to the ISS, but that was too big to fit, and too complex to ask astronauts to handle in addition to their other duties.

 

Instead, Emerald will express and purify the proteins, and then ship them to Protein BioSolutions with protocols for building 36 identical pairs of labs on chips, with each chip holding 200 different configurations of pH, salinity and other environmental factors. The chips will be immediately frozen, with one of each pair sent to the ISS and the other 36 sent to Emerald as controls. (The launch was slated for April as of the writing of this article.)

 

The chips will be thawed and the astronauts—as well as scientists on Earth—will observe what happens. After about six months in space, the samples will be returned to Earth.

 

“For any structures that actually grow in space, we will be performing X-ray diffraction on those,” Abe said. And then chemists associated with the Broad will work to identify potential therapeutics that could bind with those proteins, either to prevent their formation, or block or otherwise modify them.

 

This does not mean that protein production or other aspects of drug development will have to occur in space; rather, it will allow people to discover important information they can use in terrestrial study and production. Nevertheless, this experiment will be a test in another way: of how valuable “a potential market demand for doing early-stage drug discovery work in a microgravity environment” might be, Abe said, noting that this new opportunity could help the ISS remain scientifically and budgetarily viable.