↓ Expand ↓

Category → Uncategorized

A blogging siesta

The Siesta, by Vincent van Gogh, was painted in 1890. Credit: Wikimedia Commons

The Siesta, by Vincent van Gogh, was painted in 1890. Credit: Wikimedia Commons

Hello Artful Science readers,

As you’ve probably noticed, Artful Science has been on hiatus for a few months while I’ve been on a research sabbatical and then working on other projects.

It will continue to be on pause until further notice but I hope to resume a new incarnation of Artful Science’s cultural heritage coverage sometime in the not-so-distant future.

In the meantime, I often tweet about research on art and artifacts, should you wish to follow me in the land of Twitter.

All my best from Berlin and thanks for reading,

Sarah

This Week on CENtral Science: Happy #chemvalentine Day!

Your #chemvalentine tweet of the week:

It’s been a pretty quiet, snow-filled week at the network:

Newscripts: Amusing News Aliquots

The Watch Glass: Valentine’s Day Potpourri and tissue-engineered Olympic rings and Olympic Science

Not Part of Generation Sputnik? What’s Your Chemistry Set?

C&EN’s managing editor, Robin Giroux, sent around the following email to the staff (shared with her permission):

Folks,

If you were drawn to science/chemistry when you were young, and you’re not one of the Sputnik generation (like I am), what was that intrigued you? What drew you in?

For my generation, the response is a resounding, “I had a chemistry set.” (And if you don’t believe me, read just the Feb. 10 ACS National Award vignettes!)

That made me wonder, was there a “chemistry set” for younger generations? If so, what?

So I’m asking the question of you – and feel free to ask others outside of C&EN – but I need to hear from you by next Tuesday (Feb. 11).

And tell me, if you will, how old you are, you can use “–ish”. (I won’t share, I won’t laugh, but I may be amazed :))

Thanks!
Robin

So I’m asking others outside of C&EN – what intrigued you and drew you into chemistry? Share in the comments below or send a note to Robin at r_giroux at acs.org.

For me (Yes, yes — I know I’m not a proper chemist, but I’ll still share), it was the hands-on experiments in my high school chemistry classes.

State of the Vibe

I’ll share the gist of my Informex talk, which was entitled State of the Vibe in Pharma Chem or When New Worlds Collide. I spoke using PowerPoint slides, which I had never done before. Having seen hundreds of PowerPoint presentations, however, I knew that they had to begin with a “Forward-Looking Statement”, something to get the speaker or the speaker’s employer off the hook. So, I led the presentation with my own forward-looking statement, a quote from the German poet, Rainer Maria Rilke:

 “The truth is buried under a pile of facts.”

I can’t find where Rilke actually says this, but who else would say such a thing?

reblog 6

Thus covered, I went into an introduction of the magazine, beginning with a review of our cover stories on pharmaceuticals and fine chemicals from 2013. These showcased important themes. We covered the push toward services in contract manufacturing, the reevaluation of markets in fine chemicals, and the rise in biosimilars. Our annual case history explication of the mechanics of contract manufacturing had its crowd-pleasing focus on the drug molecules in question. There was a uniquely comprehensive feature on the quest for cures for rare diseases (a highlight of C&EN’s coverage last year, written by Lisa Jarvis). Then, there was the Pharmaceutical Year in Review, a look at what we called “The New Machine”.

As for inside action, we ran features on China, where the long-running story of low-cost competition and its down side is nuanced by the anti-corruption push of the new five-year-plan. There was an article on the push to bring excipients into the fold of regulated manufacture, largely as a means of securing the supply chain and the businesses of Western suppliers of bulk drug material. And there was one on the reemergence of Design of Experiment, the statistics-intensive industrial quality regime from the 1960s that is currently riding the wave of data analysis in science-based (certainly in pharmaceutical-based) industries.

I pointed to only one news story from 2013—DSM’s announcement last month of a deal with Patheon to create a separate company combining DSM’s pharmaceutical fine chemicals and Patheon’s formulation services businesses. A quick look at the number of diversified chemical companies who have somehow entered and exited the field of fine chemicals between the mid 1990s and 2000s has us wondering whether DSM will somehow join the club, leaving BASF as the sole diversified chemical giant still in the pharma chemical game.

Brussels 2003: "Optimism amidst the downturn," and the best photo I have ever taken--RM

Brussels 2003: “Optimism amidst the downturn,” and the best photo I have ever taken–RM

Next: A swing through ten years of fine, custom, and contract manufacturing in the pharma sector with a look at the CPhI headlines from 2003 to 2013. Long story short, we watched the sector rise steadily from a prolonged slump in the early 2000s, only to gain real traction at the beginning of a worldwide recession in 2008. Despite claims that pharma operates on its own economic cycle, we found the pharma chemicals sector in another ditch, a tough one, from which it has risen over a relatively short space amidst real optimism for the future. That optimism was in evidence not only at CPhI in Frankfurt last November, but also on the exhibit floor of Informex in Miami.

R&D Investment Plummets--Source: IMS Institute for Healthcare Informatics

R&D Investment Plummets–Source: IMS Institute for Healthcare Informatics

Turning to the recent (five-years) evolution of the pharma sector, my first slide  questioned any optimism having to do with pharmaceuticals. It showed a precipitous drop in R&D investments 2013, caused primarily by a big drop in Phase I trials. Quoting from IMS Institute for Healthcare Informatics, I noted that global drug sales grew a mere 1.3%, to $854 billion, in 2013 compared with 3.5% growth the previous year. With the five-year consolidated annual growth rate up to the present totaling about 4.5%, it’s fair to say that the pharma industry, after all it has done to reinvent itself following the blockbuster bust and in preparation for the 2012 patent cliff, had a terrible 2013. The new machine, as we called it in the C&EN Pharmaceutical Year-in-Review article, may need a little more runway before takeoff.

I ran down the checklist of features characterizing the new world in pharmaceuticals, which includes the development of complex molecules, the push for personalized or targeted therapies, and the outcomes focus of regulatory reform. Drug companies, regulators, and payers are currently scrambling to develop means of determining and communicating the value of a new chemical entity—the only point of agreement is that scientific innovation will not be the determining factor. The future seems headed toward more complex molecules required in small volumes, one in which the major pharma companies will play a drastically different role vis-a-vis emerging companies and biotechs. It is the latter who dominated the M&A action last year, with big pharma dropping from a 70% share in the deals in 2011 to less than 10% in 2013, according to Ernst & Young. Notably, one of the biggest deals in 2013 was Shire’s acquisition of ViroPharma—a $4.2 billion investment in a portfolio of drug candidates for rare diseases. The biggest deal was Amgen’s $10.2 billion acquisition of Onyx. All right, Amgen is more like big pharma than biotech these days. One of my bullet points, “Big Pharma as Bit Player?”, may have been an enormous exaggeration. For effect.

Source: Ernst & Young

Source: Ernst & Young

The push for patient data finds many of these large drug companies, who are notably in sparse attendance at Informex, forming unique partnerships. Merck, for example, is working with the Regenstreif Institute, a nonprofit medical informatics and health care research organization affiliated with Indiana University School of Medicine. The partners are studying patient health outcomes in the area of osteoporosis with data culled from Regenstrief’s information on 13 million patients. AstraZeneca is signed with HealthCore, the health outcomes research subsidiary of WellPoint, a big managed-health-care firm that keeps a huge database culled from the 44 million patients it covers. C&EN noted this year that Humedica, founded in 2008 by former pharmaceutical executives to conduct drug effectiveness studies, has seen a big rise in outcomes research, which now accounts for 40% of its business.

Moving on to the new world of fine chemicals, I noted the push for high tech chemistry and processes, which was mentioned as early as the 2003 CPhI feature as a strategy for rising from the trough. Services extending to R&D have been an obvious trend of late, also dating back several years. The development of generics is an ongoing trend, as is the reevaluation of markets: The economics elsewhere seem a lot better and always have, as this chart from Ann Thayer’s feature on fine chemicals for 2013 makes clear.

Comparative costs of bringing a new chemical entity to market. Source: Pharmaceutical Research & Manufacturers of America, CropLife America, Nat. Rev. Drug Discovery 2010,  DOI: 10.1038/nrd3078

Comparative costs of bringing a new chemical entity to market. Source: Pharmaceutical Research & Manufacturers of America, CropLife America, Nat. Rev. Drug Discovery 2010,
DOI: 10.1038/nrd3078

Then, there is the new twist on China. I noted that while there are many accounts (100% of them anecdotal) of projects gravitating back to the west because of quality concerns in Asia, several companies, including Asymchem, Porton, and Wuxi Apptech, have established themselves as alternatives to the West operating at Western standards in China. Of interest this year is a new anxiety—President Xi has made clear that the country intends to crack down on corruption, which in the huge country’s Byzantine regulatory environment will be no mean feat. Companies operating there have expressed some concern that Western firms will be targeted with arbitrary suits. The travails of GlaxoSmithKline, accused of paying doctors to prescribe drugs, is held forth as an example. But we know of several Chinese firms that have similarly been visited by investigators. A bit more volatility in China these days, to say the least.

Looking at recent action in the fine chemicals area, I made a point of what one company, Axyntis, has done over the last year. Axyntis formed a partnership with a Japanese silica specialist, Fuji Silysia Chemical, to acquire Kyralia, a chromatography services firm that Axyntis has contracted with previously. Kyralia’s assets will be moved to Axyntis’s plant in Pithiviers, France, and it will operate as a company called Kyrapharm. Axyntis also formed a Partnership with Provence Technologies Group, an R&D services firm focused on scouting chemical synthesis pathways, process design, and analytics. The partnership is intended to link early-stage drug development services to industrial-scale manufacturing at the company’s plants in France. Axyntis also acquired a plant in Calais, France, from International Chemical Investors Group, a German holding company that acquired it only a year ago from the Belgian firm Tessenderlo. Partnership, acquisition, analytical and R&D services, capacity expansion…Axyntis touched a lot of bases last year.

Markus Blocher, CEO of Dottikon, in his booth at Informex. Photo: RM

Markus Blocher, CEO of Dottikon, in his booth at Informex. Photo: RM

The poster boy for high tech chemistry and process design in my speech, somewhat randomly chosen from a large cast, was Dottikon Exclusive Synthesis, which has spent 12% of annual revenues on R&D over the past three years in preparation for the emerging upturn in business, according to CEO Markus Blocher. “The actual work is coming,” he said at CPhI in regard to process engineering services. “A new phase is just starting in pharmaceuticals, and anything that was put off into the future has to be done now.”

Some statistics supporting the rise of formulation services: More than half of the new pharmaceutical compounds moving into development have tricky physical properties. An industry-sponsorted report by Nice Insights, detailed in C&EN’s coverage in 2013, revealed that 82% of drug industry respondents believe that innovative dosage formulation is required to meet the needs of pharma R&D.

58% outsource dosage form development and 56% report that they spend $10- to $50 million on it annually.  With 30- to 40% of drugs new drugs having problems with water solubility, moisture sensitivity, or acid sensitivity, there is a booming market for services.

Hovione, Solvias, Catalent, Siegfried, and others have been building this kind of business. DSM is obviously now in the formulation service sector on a large scale.

evonik-arthurmebius2

Bringing the new world of pharmaceuticals and the new world of fine chemicals together, we will find no overall match or miss-match, obviously. The individual supplier will have to show certain specific assets, physical and scientific, to meet very specific needs of the customer. The Evonik ad above illustrates the situation nicely. But in nearly all cases, those needs will trend toward smaller-volume production of higher-value, more complex molecules. A flexible response, based on large- and small-scale manufacturing and a menu of in-demand chemistry, will be required as molecules move through development and to the market. And the drug industry’s focus on the patient will impact the volume and scientific nuance of the business available to contract suppliers of chemicals and services. The new worlds will collide at many different junctions amidst various failures to connect.

But wait. What about those down numbers for the pharma industry last year? Could all of this high-tech momentum and enthusiasm be for naught in the face of an inevitable cyclical downturn in the fine chemical sector, one that may already be underway? Will we hear the specious argument of “this cycle is different” from those attempting to maintain the high at next year’s CPhI? Who knows? Well, it’s always worth asking James Bruno, president of Chemical and Pharmaceutical Solutions, a prominent industry watcher. “I think 2014 is probably going to be a good year for most people, but those are the guys that started preparing for it in 2010, 2011,” he told me in an interview for our recent World Forecast feature a few weeks ago.

In summation, I would describe the State of the Vibe in Pharma Chem as solidly optimistic in the face of some worrying numbers in the far-from-booming pharmaceutical sector

Everyone reconvenes for DCAT Week in New York in March. Not much could change between now and then, one would think. And that’s a good thing for fine chemicals in the New World.

I have broken blog protocol on length here. I will try to keep it down next time. Thanks to the folks who showed up for my talk last Wednesday!

C&EN Talks at Informex

Informex, if somewhat downsized, was upbeat in Miami. I haven’t got official word from UBM on attendance, but the consensus on the exhibit floor was that floor walking was down. Business, however, was up! David Ager, principle scientist with DSM, said it was well worth the travel to South Beach for the leads his company picked up. Others said the same. Generally, spirits were higher in Miami than they were in Anaheim last year. Go figure.

If there was any upside to last year’s venue, it was the proximity of hotels to the convention center. Informex 2013 was like an alternative Disney World behind the real Magic Kingdom with all the hotels on a short road that ended in a cul-de-sac fronted by the convention center. Most attendees spend all week at those hotels and at the exhibition. Still, show management had a hard time getting people from the exhibit hall to rooms in the hotels for the conference sessions. The solution this year was to combine the two with presentations given at two “Silent Theaters” in the exhibit hall.

C&EN presented two of the session. Publisher Kevin Davies gave a presentation entitled “The Chemistry of Next Gen Sequencing”. And I gave one entitled “State of the Vibe in Pharmachem”. From the speaker’s perspective and the attendee’s, I thought the speaking theaters, in which the audience wore sound canceling headphones, worked very well. Most speakers drew good crowds.

Kevin Davies and the New Machine. Photo by Rick Mullin

Kevin Davies and the New Machine. Photo by Rick Mullin

Kevin’s talk was intriguing. A history of the genome and its sequencing from Sanger, the genomics pioneer, to Illumina, the firm that debuted the much anticipated $1,000 genome just this month. There were walk-ons by Watson and a Dutch woman whose name approximates Crick. Much scientific intrigue, if not your standard chemistry.

Kevin is an authoritative source on the $1,000 genome, having, in fact, written the book. His slide headings were fantastic—The Language of God, The Book of Life, and Mission Accomplished [with a photo of George W. Bush on deck under the banner for context]. He walked us, engagingly, through the rise of single molecule exonuclease sequencing, the emergence of companies like Solexa and Illumina, and the efforts and machinations of marvelously driven characters such as Jonathan Rothberg and Craig Venter. He showed us scientist pub life in Cambridge, UK, and the rise of Oxford Nanopore, which recently debuted a sequencing device about the size of a matchbox car, heralding the easy-access sequencing of our X-topian future. Kevin demonstrated this thingamabob at the bar last night, and it is quite amazing.

 It is all very amazing. Especially the competition between scientists and the companies they form, reminding us that advances in pharmaceutical science have historically been heavily fueled and impeded by matters pertaining to fame and money. OK, certainly there is a legitimate drive for cures in the engine. But there are also some tough considerations as genome sequencing comes within the broadest public reach. Kevin’s presentation raised the equation of the $1,000 genome and the $1 million interpretation. He noted that there is much wailing over the FDA holding things up at 23andMe, a company that made waves five years ago when it began marketing rapid genetic testing to the rich and interested. But it may not be such a bad thing for 23andMe’s service to be regulated. Moreover, it’s important to note that their service produces genetic data that is pretty tough to vet and, therefore, may not tell the customer all that much.

Kevin is a real expert on all of this and he’s given me a few leads for the Life Science Business feature due on February 24. In that article, I will be looking at the RE-SET button being pushed on personalized medicine. Over the next couple of weeks, I will be learning a lot more about where genomics data ends and where patient data starts in the near-future world of drug research. Have any ideas? Call me.

In Silent Theater 1: State of the Vibe. Photo by Peter Cutts

In Silent Theater 1: State of the Vibe. Photo by Peter Cutts

My presentation covered the transformation that has occurred in the pharmaceutical and fine chemical sectors and how well the latter has accommodated the former. I drew heavily from the Pharmaceutical Year in Review issue of C&EN (December 9, 2013) and the headlines C&EN ran for its CPhI coverage over the last ten years. I will flesh that talk out in my next post… this one is getting long.

Buh-buh-buh-buh-buh-Bad!

With Donna Nelson before her presentation at Informex. Photo by Kelly Quigley

With Donna Nelson before her presentation at Informex. Photo by Kelly Quigley

Today I was offered a great opportunity to air my grievances about Breaking Bad, the award-winning AMC dramatic series that I have avoided watching. As it turns out, I’m glad I waited until now! Donna Nelson, a chemistry professor at the University of Oklahoma who has garnered a bit of fame in the chemistry world as a consultant for the series, was the opening speaker at Informex this morning. I hit her with my reservations regarding the show, more-or-less like a ton of bricks, moments before she got started.

My reservations, I told her, arise from the following perceptions:

1)   Science nerds (we will visit the word nerd below… relax) took to the show with immense enthusiasm for living vicariously through an outlaw chemist—an outlaw chemist who is making crystal meth for money!

2)    The science enterprise latched on to this show’s popularity as a chance to finally get science right on TV with a show… about making crystal meth!

3)   A fundamental question: What do the details of chemistry have to do with drama? I never cared about the authenticity of Carmella’s recipe for tomato gravy when I watched the Sopranos (twice) because it had nothing to do with the drama. I doubt David Chase brought in a chef to consult. Why should I be interested in the details of the chemistry in Breaking Bad when it is the dramatic element of how the chemistry is used that should hook me?

In my view the Chemical Enterprise has shown too much enthusiasm for a story of science’s amorality tipping heavily into the immoral. What kind of anti-hero role model is Walter White?

Nelson effectively disarmed me in our brief chat before she went on. I could tell intuitively that she saw something behind the kind of objections I raised, objections comparable to those of colleagues who pulled her aside when she got started and said… “Do you know what that show is about? Don’t do it!”

She did it, and I’m impressed with what she’s done. And C&EN had a bit roll in her contribution to the Enterprise as a volunteer adviser on chemistry:

Nelson saw a story in C&EN written by Jyllian Kemsley in which Vince Gilligan, the show’s writer and producer, told her he would very much welcome input from chemists. The story ran after the first few episodes. Nelson decided to take him up on it, and got an introduction through Rudy Baum, then editor-in-chief of C&EN. Nelson says she was satisfied that the series did not glorify illicit drug production—she tells me that the protagonist is dragged through the desert in his underwear, among other degradations, and is finally (spoiler alert) killed. She added that the U. S. Drug Enforcement Agency also consulted on the show, advising on the look and feel of a real bathroom meth lab and making sure that the series did not broadcast a recipe for making the drug.

Well, OK. Walter is portrayed as a bad guy who gets his comeuppance. Just like Jesse James, who is still considered a mythic hero. Nelson, in fact, showed in her presentation that students in the Oklahoma University Affiliates of the ACS ran around with T shirts that said, “We do stuff in labs that would be a felony in your garage!”

(Science nerds living vicariously through an outlaw chemist, etc.: Check).

But Nelson alerted me to a practical consideration having to do with the science community communicating with the public. Think about it—C&EN broadcasts a request for a scientist to consult with Hollywood on a hot new TV series. How many chemists respond? One. Just one! Donna Nelson. Think also about how many TV shows and movies involve science. Now, how many producers put out the feelers for real scientists to consult? Well who knows? But only one has done so through C&EN. Gilligan, a professed amateur science nerd, deserves a lot of credit for reaching out. And he had a hard time finding a response. Nelson, who flew to Burbank, Calif., for an initial meeting, expressed some shock that the show got no input from any of the nearby universities. Gilligan said they all snubbed him. Nobody wanted to risk getting involved.

Nelson took a pragmatic view of her options. “They had a hit,” she told me. “It was either going to be a hit with good science or a hit with faulty science.”

I appreciated Nelson’s willingness to listen by my spiel about how the science community is its own worst enemy when communicating with the public. She agrees with me! Such communication is all about taking the kind of risk she took in getting the blackboard in the classroom right on a TV show. Getting the dialogue right. Getting the reactions straight. Apparently they loved her at Breaking Bad. They relied on her heavily, and the show benefited greatly. So did chemistry. It worked because chemistry became an integral aspect of the drama.

Since working on Breaking Bad, Nelson has appeared on panels with writers and actors from shows like CSI, House MD, and others that deal with science and medicine.

There is no lack of science in popular entertainment. And entertainment is pervasive in our culture. Think of TED Talks. TED stands for Technology, Entertainment, and Design. These are presented as the pillars of highbrow contemporary discourse! I much prefer an edgier venue called Nerd Nite, which is probably an even more entertaining venue for science. Nelson says she hopes to dispel the notion that scientists are nerds, and here may be the one area on which we disagree. The term nerd is now synonymous with hip in the good sense of hip. Nerds are smart and cool. Nerds are nothing like the elitist science hermits I’ve seen giving TED talks or the ostensibly non-nerd folks in the audience at these things.

Maybe the real outlaw, the one with the white hat in Breaking Bad, is Donna Nelson. What a step she has taken outside the collective comfort zone! Even if my dystopian vision of a future in which chemists on the cover of C&EN have to wear ski masks along with their protective eyewear and lab coats is realized, we know from Nelson’s example that science can be communicated accurately and entertainingly to a broad, really quite smart audience.

Ohhhhhhhhh~ Miami!

Informex got off to a glorious start last night with a cocktail reception at the Skydeck here in Miami. So far, the big story is that the annual conference and exhibition survived being in Anaheim last year, a choice of venue that I like to think of as a kind of ironic joke at my expense.

We are only getting started, with the day of business and technical presentations that precedes the exhibition hall days at Informex. The event, now organized by UBM Live, is celebrating its 30th anniversary this year, by the way–a testimony to the strength of the fine chemicals community within the “Chemical Enterprise”. This is in no small part thanks to the efforts of the Society of Chemical Manufacturers and Affiliates, which, when it was the Synthetic Organic Chemical Manufacturers Association, introduced Informex in, I believe, Atlanta (a few card tables and I think you were allowed to smoke). SOCMA grew Informex to fill a sizable exhibit hall every year, regularly holding it in New Orleans for a good stretch before handing the reins over to UBM.

Which reminds me of a cab ride in Las Vegas when Informex hit that city some years back. My cab driver asked what show I was in to see.

Me: Informex. It’s the Synthetic Organic Chemical Manufacturers Association meeting.

Driver: Oh.

Driver [following ten minutes of silence]: Can a chemical be synthetic and organic?

Me: Good question.

I was particularly impressed today with Maximillian Yeh’s presentation on highly-potent active ingredients. Yeh is a North American account director with Evonik based in San Francisco. I also liked the talk Stephen DeSalvo, the U.S. marketing director of Fabbrica Italiana Sintetici  (FIS), gave on that company’s recent investments in everything from an anti-cancer active pharmaceutical ingredients pilot plant to Delmar Chemicals, an API producer near Montreal. FIS, with headquarters and primary manufacturing in Vicenza, Italy, is investing heavily in building Delmar into a North American sister site with capabilities similar to those it has in Italy.

The two talks touched on themes that are dominant now in the fine chemicals sector—specialization and expansion. I will be giving a talk tomorrow at 3:00 pm in “Theater 1” at Informex titled, “State of the Vibe in Pharma Chem”. In it, I will expand on these two themes and others as I gloss the changes in the pharmaceutical sector and those in the field of fine chemicals.

Skip at the Skydeck reception.

Skip at the Skydeck reception.

One delightful surprise so far was a visit from Walter “Skip” Mongen, a sales executive with C&EN for many years who retired about five years ago. Skip hit the Skydeck on Monday. We reminisced about the night we got lost walking back from a restaurant in Madrid doing a shabby Abbott and Costello imitation as we got even more lost. And then there was that dinner in Milan…. Ah, the memories.

Cultural note: I may have jinxed the weather here slightly by cuing this on my iPod as I hit the causeway. But who wouldn’t put on Donald Fagen’s swing-bop tribute upon entering these environs?

More tomorrow! And come to my talk at 3:00 pm, Theater 1, if you’re on site.
___________

My colleague Ann Thayer is “tweeting” here. To follow Ann’s tweets from Informex, reference: @annmthayer

 

This Week on CENtral Science: chemistry sets, lab safety culture and more

Tweet of the Week:

 

On to the network:

Newscripts: Amusing News Aliquots and Heirloom Chemistry Set and In Print: Balloon Returns Home, Earthshaking Stadium

The Safety Zone: CSB report on Chevron refinery fire urges new regulatory approach and Assessing changes in lab safety culture and Is academic lab safety culture improving?

The Watch Glass: Toys—Growing Outlet for Plastics and Flu Fighters and Chemistry Sets (1970) and Antifreeze Proteins Help Snow Fleas Get Through Winter