I've recently been working to unearth the scientific genealogy of Carlos Bustamante's lab. With the aid of some labmates, we have made quite a bit of progress! We have the lineage to the 17th century, and it goes thusly:

Carlos José Bustamante

• 1951-present
  
• Ph.D. in Biophysics, University of California, Berkeley, 1981
  

• 1930-present
  
• Ph.D. University Wisconsin, 1954
  

• 1912-2003
  
• Ph.D., Stanford University, 1935
  

• 1894-1966
  
• Ph.D., University of California, Berkeley, 1919
  

• 1884-1959
  
• Ph.D., Universität Breslau, 1911
  
• [California Digital Library]
  

• 1860-1925
  
• Ph.D., Universität Berlin, 1884
  
• Dissertation: Über eine neue Interferenz-Erscheinung an planparallelen Glasplatten und eine Methode die Planparallelität solcher Gläser zu prüfen
  

• 1821-1894
  
• M.D., Königlich Medizinisch-chirurgische Friedrich-Wilhelm Institut, Berlin, 1842
  
• [Max Planck Institute for the History of Science]
  

• 1801-1858
  
• M.D., University of Bonn, 1822
  
• [Max Planck Institute for the History of Science]
  

• 1771-1832
  
• M.D., Ernst-Moritz-Arndt-Universität Greifswald, 1795
  
• [MGP]
  

• 1748-1831
  
• Georg-August-Universität Göttingen, 1771
  
• [MGP]
  

• 1744-1777
  
• Georg-August-Universität Göttingen, 1767
  
• [MGP]
  

• 1719-1800
  
• Ph.D., Universität Leipzig, 1739
  
• Dissertation: Theoria radicum in aequationibus
  
• [MGP]
  

• 1693-1743
  
• Ph.D., Martin-Luther-Universität Halle-Wittenberg, 1713
  
• Dissertation: De corpore scissuris figurisque non cruetando ductu
  
• [MGP]
  

• 1663-1727
  
• Ph.D., Universität Leipzig, 1685
  
• Dissertation: Disputationem Moralem De Divortiis Secundum Jus Naturae
  
• [MGP]
  

• 1644-1707
  
• Ph.D., Universität Leipzig, 1665
  
• Dissertation: Ex Theologia naturali — De Absoluta Dei Simplicitate, Micropolitiam, id est Rempublicam In Microcosmo Conspicuam
  
• [MGP]
  

Filed under biology · chemistry · physics · science · science history

Posted by H. C. Hodges at 11:19 AM | Permalink | Comments (1)

Getting the cover of a journal like Nature is a little bit like winning the scientific lottery. So we're very proud:

Congratulations all around, especially to Jin-Der, who has done a fantastic job of making this project work. Although we were the first to observe ribosome activity in real-time, there is so much yet to come!

Filed under berkeley · biology · chemistry · physics · science

Posted by H. C. Hodges at 10:23 AM | Permalink | Comments (2)

It's been a slow couple of months here at HodgesLab. Our ribosome paper was accepted into Nature, and they have also given us another surprise. Check back on April 2.

Filed under science

Posted by H. C. Hodges at 10:06 AM | Permalink | Comments (0)

This makes me sick to my stomach:

After 27 years as a science teacher and 9 years as the Texas Education Agency’s director of science, Christine Castillo Comer said she did not think she had to remain “neutral” about teaching the theory of evolution.

“It’s not just a good idea; it’s the law,” said Ms. Comer, citing the state’s science curriculum. But now Ms. Comer, 56, of Austin, is out of a job, after forwarding an e-mail message on a talk about evolution and creationism [...]

Her departure, which has stirred dismay among science professionals since it became public last week, is a prelude to an expected battle early next year over rewriting the state’s science education standards, which include the teaching of evolution [...]

The chairman of the panel, Dr. Don McLeroy, a dentist and Sunday School teacher at Grace Bible Church in College Station, has lectured favorably in the past about intelligent design.

Having gone to school in College Station, I am familiar with Grace Bible Church. It's a very, very family-friendly evangelical church. I knew a lot of kids who went there, and they were definitely the classic evangelical type. I suppose that's beside the point; the real question is: how the hell is a dentist and Sunday school teacher heading up the panel for the TEA's standardized science curriculum? Is there really no better qualified person in the entire state of Texas? A trained scientist perhaps?

From the article, it isn't clear the text of the email that Comer sent out. Was it like "FYI -- attached message" or was it like "FYI -- let's get these creationist nutjobs!" (the difference is huge; while the former would be lawsuit worthy, the latter would obviously be grounds for disciplinary action).

In any case, I'm nervous that Texas will retreat from the required teaching of modern biology in school. Words cannot express how angry it makes me that we still have to debate the single unifying core tenet of modern biology. It's like "debating" GR. Ugh.

Filed under biology · evolution · intelligent design · science · texas · textbooks

Posted by H. C. Hodges at 11:30 AM | Permalink | Comments (2)

Recently, a group of student-organized protesters picketed on-campus and outside the Helen Wills 10th anniversary symposium. The Helen Wills Institute is a neuroscience institute with affiliated labs on the Berkeley campus. Most of the animal protesters wore bandanas over their faces and carried signs like "vivisection kills" and wrote on the sidewalks phrases like "animals die while demons rejoice." I have come to the conclusion that protesting like this is an unhelpful contribution to on-campus activism as well as a distraction from a fruitful animal-research debate.

Continue reading "Vivisection at Berkeley: Protest all life sciences!" »

Filed under animal studies · berkeley · biology · cancer · hiv · mammals · science · stem cells

Posted by H. C. Hodges at 2:52 PM | Permalink | Comments (7)

I was reading a blog today wherein a professor made a post about the scientific support for evolution, and the lack of such support for intelligent design. He pointed out:

[Y]ou can access the websites of any major scientific organization [...] to read their statements affirming evolution as the unifying theory of biology and the disaffirming of all forms of creationism including intelligent design.

Although news organizations seem to be recognizing the false controversy stirred up by ID proponents in order to advance their political goals, it is still easy to be given the impression that there remains some controversy amongst learned scientists on the issue. So I was curious how clear scientific organizations have been in condemning "intelligent design" as pseudo-science.

I checked the largest, most influential and most recognized scientific organizations; below are their official statements on intelligent design and evolution:

• The National Academy of Sciences (NAS) — publishes The Proceedings of the National Academy of Sciences (PNAS), official organization that advises the US President on matters of science and technology [ref]:

  Creationism, intelligent design, and other claims of supernatural intervention in the origin of life or of species are not science because they are not testable by the methods of science [...] Documentation offered in support of these claims is typically limited to the special publications of their advocates. These publications do not offer hypotheses subject to change in light of new data, new interpretations, or demonstration of error. [...]
  
  No body of beliefs that has its origin in doctrinal material rather than scientific observation, interpretation, and experimentation should be admissible as science in any science course [...] Science has been greatly successful at explaining natural processes, and this has led not only to increased understanding of the universe but also to major improvements in technology and public health and welfare. The growing role that science plays in modem life requires that science, and not religion, be taught in science classes.

• American Association for the Advancement of Science (AAAS) — world's largest scientific organization, publisher of Science magazine, quite possibly the world's most widely respected peer-reviewed scientific journal [ref]:

  Over the past several years proponents of so-called "intelligent design theory," also known as ID, have challenged the accepted scientific theory of biological evolution. As part of this effort they have sought to introduce the teaching of "intelligent design theory" into the science curricula of the public schools. The movement presents "intelligent design theory" to the public as a theoretical innovation, supported by scientific evidence, that offers a more adequate explanation for the origin of the diversity of living organisms than the current scientifically accepted theory of evolution. In response to this effort, individual scientists and philosophers of science have provided substantive critiques of "intelligent design," demonstrating significant conceptual flaws in its formulation, a lack of credible scientific evidence, and misrepresentations of scientific facts.
  
  [...] AAAS calls upon its members to assist those engaged in overseeing science education policy to understand the nature of science, the content of contemporary evolutionary theory and the inappropriateness of "intelligent design theory" as subject matter for science education

• National Science Teacher's Association (NSTA) — the largest organization in the world committed to supporting science teaching, membership of more than 55,000 including science teachers, science supervisors, administrators, scientists, business and industry representatives [ref]

  The National Science Teachers Association (NSTA) strongly supports the position that evolution is a major unifying concept in science and should be included in the K-12 science education frameworks and curricula. Furthermore, if evolution is not taught, students will not achieve the level of scientific literacy they need [...] NSTA also recognizes that evolution has not been emphasized in science curricula in a manner commensurate to its importance because of official policies, intimidation of science teachers, the general public's misunderstanding of evolutionary theory, and a century of controversy. In addition, teachers are being pressured to introduce creationism, "creation science," and other nonscientific views, which are intended to weaken or eliminate the teaching of evolution.

• The American Physical Society (APS) — the APS is the leading American professional body of physicists, and represents over 46,000 physicists in academia and industry in the US and internationally [ref]

  Marvin Cohen, president of the American Physical Society (APS), has stated that only scientifically validated theories, such as evolution, should be taught in the nation’s science classes. He made this statement in response to recently reported remarks of President Bush about intelligent design, which is a type of creationism.

• The American Geophysical Union (AGU) — an organization of 43,000 Earth and space scientists; publishes a dozen peer reviewed journal series as well as scientific meetings [ref]:

  Scientific theories, like evolution and relativity and plate tectonics, are hypotheses that have survived extensive testing and repeated verification. Scientific theories are therefore the best-substantiated statements that scientists can make to explain the organization and operation of the natural world. Thus, a scientific theory is not equal to a belief, a hunch, or an untested hypothesis [...] "Creation science" is based on faith and is not supported by scientific observations of the natural world. Creationism is not science and does not have a legitimate place in any science curriculum. AGU opposes all efforts to require or promote teaching creationism or any other religious tenets as science. AGU supports the National Science Education Standards, which incorporate well-established scientific theories including the origin of the universe, the age of Earth, and the evolution of life.

• The American Astronomical Society (AAS) — membership of 6,500 scientists including physicists, mathematicians, geologists, engineers and others whose research interests lie within contemporary astronomy [ref]

  A small, but vocal, minority of religious individuals has been urging a major revision of how evolution is taught in U.S. schools. Based on the personal beliefs, they find fault not only with biological evolution, but also with modern astronomical ideas about the age, expansion, and evolution of the universe. They have been actively pressing their case in the political, media, and educational arenas, and their loud arguments sometimes drown out other perspectives, including science [...] Not only is evolution a unifying concept in biology but also describes the way in which the planets, stars, galaxies, and universe change over long periods of time [...] Research [...] has produced clear, compelling and widely accepted evidence that astronomical objects and systems evolve [...] Specifically, the scientific evidence clearly indicates that the Universe is 10 to 15 billion years old, and began in a hot, dense state we call the Big Bang.

• The American Chemical Society (ACS) — the leading, self-governed organization that consists of more than 160,000 members at all degree levels and in all fields of chemistry [ref]

  Evolutionary theory is not a hypothesis, but is the scientifically accepted explanation for the origin of species, and explains significant observations in chemistry, biology, geology, and other disciplines [...] Evolution cannot be dismissed or diminished by characterizing it as mere conjecture or speculation. Scientific explanations of the natural world have been reached through observation and experimentation, are testable through observation and manipulation of natural systems, and can be modified as a result of new information. The inclusion of non-scientific explanations in science curricula misrepresents the nature and processes of science.

• Federation of American Societies for Experimental Biology (FASEB) — represents 22 professional societies and 84,000 scientists in disciplines that range from single molecules to public health [ref]

  [I]t is critical to preserve the integrity of science education by opposing the mandatory teaching in science classes of creationism, intelligent design, and other concepts not based on sound scientific principles [...] Proponents for non-scientific accounts of the development of life, including creationism and intelligent design, contend that evolution alone should not be taught in science classes. Arguing that evolution is "just a theory," rather than a fact, they insist that intelligent design should be offered as an alternative to evolution or given "equal time", and that schools should "teach the controversy" surrounding evolutionary theory. FASEB does not support these views. We also affirm that these positions seriously undermine science education [...]
  
  [E]volution is categorized with other scientific theories such as gravity or atomic theory, which, like evolution, are universally accepted among scientists.
  
  Evolution is among the most thoroughly tested theories in the biological sciences. It is supported by volumes of scientific evidence in numerous fields, including genetics, biochemistry, developmental biology, comparative anatomy, immunology, geology, and paleontology. Moreover, evolution lays the foundation for much of what we know about genetics, immunology, antibiotic resistance, human origins, and the adaptation of species to a changing environment. Removing evolution from the classroom, or misrepresenting evolution as a flawed theory, deprives students [...]
  
  In contrast to evolution, intelligent design and creationism are not science because they fail to meet the essential and necessary requirements: they are not based on direct observation or experimentation nor do they generate testable predictions. Therefore, offering these beliefs as alternatives to evolution or giving them equal time in science classes completely misrepresents the nature of science [...] Proposals that call for “teaching the controversy” or singling out evolution for criticism are equally objectionable. While there may be some disagreement about the details of evolution, it is not a controversial theory among scientists. Rather, there is overwhelming scientific consensus that evolution is a valid explanation for the development of species. Although students should be encouraged to think critically about all ideas, introducing false controversy into science classes will ultimately impair science education.

There are countless more scientific organization with similar statements. As is obvious, there is no controversy in the physical, chemical, or biological sciences; the debate is one-sided, constructed by the proponents of "intelligent design" in order to justify their views. Universities, schools, and other organizations involved in education do a disservice to their students and to the public by even passively supporting these views.

Filed under biology · evolution · intelligent design · science

Posted by H. C. Hodges at 4:54 PM | Permalink | Comments (0)

This article at the NY Times is quite disappointing. The author makes several unwarranted leaps, for example, comparing the cost of vaccinations in 1980 to today...

Getting a vaccination was not always so difficult. In 1980, it cost only about $23, or $59 adjusted for inflation, for the seven shots and four oral doses needed to immunize a child, according to data provided by Thomas Saari, who is emeritus professor of pediatrics at the University of Wisconsin.

Today, though, a child who receives all the recommended vaccines would receive as many as 37 shots and 3 oral doses by the 18th birthday — at a cost exceeding $1,600.

The 1980's were well before the biotech industry really existed (hell, recombinant techniques didn't even exist until nearly the mid-70's!); one would fully expect that vaccines developed before modern molecular biology would be technologically simpler and cost less to develop and produce. Plus we're not comparing the same thing... the above compares required vaccines in 1980 with all recommended vaccines today; when you include the newer, clearly useful, vaccines, you fully expect the price to increase. So the comparison is rather disingenuous.

Note that the argument isn't about whether or not the new vaccines should be mandatory; the Times article is mostly complaining about the cost of all recommended vaccines.

There is amongst some an expectation that any biological technology that can help people should be given away for nearly free. This attitude doesn't seem to appear in other sciences (who would expect carbon nanorods, or synthetic zeolite catalysts to be immediately affordable?). Why is biology so different?

If the fear-mongering segment of the public succeeds in taking the market out of the biological technology industry, there won't be one. Let's not get so breathless when drug prices are high, because it's worth remembering therapeutics will be cheap and abundant when their patents runs out.

It's instructive to remember that Rogaine, Claritin, Aleve, and even Tylenol were all once on-patent drugs...

Filed under chemistry · patents · science

Posted by H. C. Hodges at 4:16 PM | Permalink | Comments (0)

I got this email 27 minutes ago from Robert Birgeneau, our Chancellor:

Colleagues, students, and friends:

I am proud and excited to tell you that a partnership led by UC Berkeley has been selected to receive an unprecedented $500 million from global energy firm BP to lead the way in research to develop new, clean, renewable sources of energy. With this remarkable support, the work Berkeley will undertake will be transformative for our nation and, indeed, our planet.

The campus will partner with Lawrence Berkeley National Laboratory and the University of Illinois at Urbana-Champaign in this 10-year effort, which was announced this morning at a campus press conference by Robert A. Malone, chairman and president of BP America Inc., along with Gov. Arnold Schwarzenegger and Illinois Gov. Rod Blagojevich.

This new research effort -- the Energy Biosciences Institute (EBI) -- will focus initially on biotechnology to produce biofuels, that is, transportation fuels that are made from plants. Berkeley and its partners will bring the most creative science, innovative technologies, and astute understanding of social sciences to bear to develop viable solutions to global energy challenges, among the most fundamental problems facing us today.

[...]

First thought: holy crap that's a lot of money (second thought: wow, BP is actually putting its money where its mouth is). I think this is fantastic news, not only for Berkeley, but also for energy research in general. For more information about this rather unprecedented research partnership, see here and here.

UPDATE: This article in the SF Chronicle more succinctly lays out what this all means.

Filed under berkeley · biology · energy · science

Posted by H. C. Hodges at 11:52 AM | Permalink | Comments (0)

The story in today's NY Times about Eric Poehlman's scientific fraud is definitely worth a read. Apparently, an undergraduate tech uncovered the PI's ongoing misconduct, and helped take him down... Poehlman has become the first scientist ever sentenced to prison time for falsifying data on grant applications.

Filed under science

Posted by H. C. Hodges at 12:22 PM | Permalink | Comments (0)

While a thought-provoking piece, this article from The Sun is total bullshit.

Dr Curry continues: “People of the year 3000 will have reached the peak of human enhancement, leading the longest, healthiest and most accomplished lives in the entire history of the human race.

“Improved nutrition and understanding of the human body will see people grow taller, with men reaching an average height of between six and seven feet, while lifespans will also be far greater, with humans living for up to 120 years.”

Dr Curry also claims men and women will also become better-looking by the next Millennium in order to attract a mate.

The coffee-colored thing is pretty obvious and probably true, but the expectation that we'll all be more attractive? Evolution cares only about relative differences in reproductive success, therefore humanity becoming "more attractive" or "sportin' bigger junk" is only possible if people with those traits squeeze out kids more often than those lacking said traits. From my perspective, it's not obvious that the attractive or the well-endowed are having more children...

As a result men are expected to exhibit symmetrical facial features, athleticism and the classic signs of testosterone such as a square jaw, deeper voice and larger manhood...

“Skills such as communicating and interacting with others will be degraded, leaving humans less able to care for others."

Horse shiat. Current pressures still select for the people who are sociable and outgoing. Ever try living the life of a sociophobe? It's impossible for a man to send forth his homunculi into the fertile land-o-plenty without a little social skill. What reproductive mechanism (short of mass-conception-by-donor-sperm) allows humanity to shed its need for social skills?

If we really want to breed "better" humans, humanity will have to develop a mechanism of encouraging the successful to have more children than the unsuccessful (whatever "success" means). Technology may have allowed us to decouple successful behavior from reproductive success, in which case our selection would also be inverted. If true, then natural selection ain't directly headed towards a future full of symmetrical, intelligent, coffee-colored athletes. For the purposes of our species, social pressures and access to technology are probably much more powerful predictors of reproductive success than most innate tendencies.

Filed under biology · culture · evolution · intelligent design · science

Posted by H. C. Hodges at 6:26 PM | Permalink | Comments (0)

The University of California has its hands all over the Nobels this year, in one way or another. Today it was announced that George Smoot of the Department of Physics here at Berkeley has won the Nobel Prize in Physics for astrophysical work examining the residual blackbody radiation from the early universe. It turns out his co-recipient, John Mather, also did his graduate work here at UC^(†). From the press release:

Smoot, a resident of Berkeley, was surprised by an early morning call from Sweden to his unlisted cell phone, which the Nobel committee obtained by waking his neighbor.

"There were no rumors. I figured they only give the prize when you're close to death, and I still have enough life left in me," said Smoot, 61.

This marks the twentieth Nobel Prize awarded to Berkeley faculty, and the eighth given to faculty in the Physics Department. Around Birge and Le Conte Halls, we have lots of parking spaces marked 'NL' (these are the ones allocated to the Nobel Laureates). Looks like they'll have to clear off a handicapped spot to make room for the new bigshot.

^(†) Let us not forget Andy Fire, who won yesterday for Medicine, and who is also a Berkeley alumn.

UPDATE: I almost missed this part of the press release:

In the finest tradition of Berkeley Nobelists, George is also a dedicated teacher. In addition to working with his graduate students, he currently sponsors undergraduate researchers in his lab and this semester is teaching Physics 7B, the introductory course for science and engineering majors.

Must be a heady feeling to walk into your first class as an undergrad only to find that your lecturer was just awarded the Nobel Prize in Physics that morning.

PHOTO UPDATE: The Department of Physics just held a reception in honor of Smoot's Nobel. I was standing just behind Berkeley's Chancellor Robert Birgeneau and George Smoot during the toast, so look for my bright shining face tomorrow on the Berkeley website. I also managed to snap a couple photos on the trusty camera-phone. Below, see George Smoot and 1997 laureate Steven Chu, respectively:

Filed under berkeley · physics · science

Posted by H. C. Hodges at 10:25 AM | Permalink | Comments (0)

Andy Fire (now at Stanford) and Craig Mello (of the University of Massachusetts Medical School) are newly minted Nobel laureates. Just a few years back, they discovered a process called RNA interference ('RNAi') in the nematode worm C. elegans. Nature (free link) sums it up best:

RNAi, which occurs naturally in plants and animals, allows a gene to be specifically 'silenced'. This helps to regulate gene expression, and protects against viral infection and 'jumping genes' that can replicate and spread through the genome.

The process can also be induced experimentally by injecting tailor-made genetic sequences into cells, giving scientists a method for deliberately silencing a target gene. The method is now widely used as a basic genetic tool and is a promising candidate for future therapies.

These guys deserve it, and everybody knew they'd eventually win it. Personally, I'm still a little surprised some GFP folks haven't won yet (Roger Tsien, Douglas Prasher, Marty Chalfie). GFP is used everywhere, and some might argue that it has yielded more biological insights than has RNAi. Still, the RNAi guys did some great science, and I'm glad to see them win.

UPDATE: Aggie prof Jim Hu photoblogs the press conference at Stanford for Andy Fire. Nice work.

UPDATE: Of course, Berkeley is quick to note that Fire is a Berkeley alumn.

Filed under biology · science

Posted by H. C. Hodges at 11:47 AM | Permalink | Comments (0)

As you may recall from my previous post, a company called Ariad is suing Lilly & Co. over alleged infringement of a patent related to NF-κB activity. NF-κB is a protein which regulates inflammation and immune response in cells; as such, it is considered by many to be a great target for new drugs.

In my previous post, I expressed skepticism that the so-called 'Baltimore patent' will be upheld. I have since bothered slugging through some of the patent code (U.S.C. 35), and have refined my thoughts a little more.

One of the strongest arguments I can think of against Ariad is that the Baltimore patent had simply not reduced the claimed invention to practice. According to 35 U.S.C. § 112:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

As an example, consider two fairly representative claims from the Baltimore patent:

1. A method of inhibiting expression, in a eukaryotic cell, of a gene whose transcription is regulated by NF-κB, the method comprising reducing NF-κB activity in the cell such that the expression of said gene is inhibited.

6. A method for diminishing induced NF-κB-mediated intracellular signaling comprising reducing NF-κB activity in cells such that NF-κB-mediated intracellular signaling is diminished.

Obviously creating a particular drug requires vastly more resources than claiming what amounts to a big-picture idea for a research project. The court will have to decide whether or not the Baltimore patent ever actually reduced to practice their claimed invention. It is a fundamental requirement that a patent describe an invention well enough for a person having ordinary skill in the art (of biochemistry, in this case) to be able to create and use the invention. This is what The People receive in exchange for granting an exclusive license to the inventor.

Furthermore, according to 35 U.S.C. § 102(g), Lilly need only show that it conceived of the two drugs and worked "with reasonable diligence" to create them before the priority date of the Baltimore patent. Lilly also has to show that it didn't "abandon, suppress, or conceal" those two drugs. Since Lilly claims it disclosed the medical properties of Xigris and Evista before the Baltimore inventors conceived of their idea, it will be very difficult for Ariad to show that Lilly had concealed Evista or Xigris before the Baltimore patent's priority date.

The courts must consider "not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice." Lilly, it seems to me, need only prove that they worked with reasonable diligence to reduce their two drugs to practice, while Ariad and the patent holders have to prove that they have sufficiently disclosed their invention such that any skilled worker could create and use it.

As a fairly skilled worker in the art of biochemistry, I wouldn't have any idea where to start to create and use some of the claimed inventions in the Baltimore patent. It is pretty clear to me that the Baltimore patent has not sufficiently disclosed their invention; as such I continue to expect that the appellate court will decide for Lilly & Co. and set aside the jury's previous verdict.

Filed under biology · chemistry · patents · science

Posted by H. C. Hodges at 10:31 PM | Permalink | Comments (0)

No, I don't mean that Franciscan question of whether or not animals go to heaven or hell. I mean physically, where are all the squirrel corpses? Laying aside for the moment all the squirrels I've seen run over then left as roadkill, I have never, not even once, seen a dead squirrel carcass. Isn't that weird?

Has anyone else? Where do they go? This is truly astonishing to me that, although I've seen small land mammals like squirrels, possums, and raccons alive many times, I've never actually seen one dead.

It's not like we have lots of other predators in metropolitan areas to kill, eat, and scatter their bones mercilessly... do they eat the remains of each other? Do raccoons eat the dead squirrels? I must know!

Filed under mammals · science

Posted by H. C. Hodges at 6:12 PM | Permalink | Comments (1)

I was end-labeling some RNA with ³²P earlier today and, since I didn't really want radioactive stuff on my person, I decided to wear a labcoat. It occurred to me that this was quite possibly the first time I'd ever donned such a garment since coming to Berkeley. Mind you, I have worn labcoats before (like when I used to remove brains and spinal cords from immunocompromised mice back at Jane Welsh's lab), just never here at Berkeley, and never while holding something that was as hot as a two-dollar pistol.

So obviously we decide to document the occasion. Looking suitably scientific, I visually inspect the radiolabeled RNA and ponder the yet-to-be-revealed mysteries within... science requires a lot of pondering.

Filed under science

Posted by H. C. Hodges at 2:58 PM | Permalink | Comments (2)

Turns out, quite a bit...

Via fark.com: a site with a small collection of astronomy paintings from the 19th century.

One commenter says, and I agree, that there is something about these works that reminds me a little bit of Kandinsky. Must've been something in the water back then. Pretty cool stuff.

Filed under art · science

Posted by H. C. Hodges at 7:11 PM | Permalink | Comments (1)

GWB's stem-cell veto threat makes me too frustrated to say anything intelligent. It would mark his first veto EVER, and on a topic that about 70% of Americans support. Asshat.

Filed under biology · science · stem cells

Posted by H. C. Hodges at 3:22 PM | Permalink | Comments (0)

Last night, I read an old paper by Ernst Mayr on the position of biology amongst the sciences (Quarterly Review of Biology, 71(1): 97-106, 1996). In it, he posits that biology is rather radically different from other physical sciences; as a result, he says biology ought to be considered an autonomous branch of science, and not a provincial branch of physics or chemistry.

This, along with a more strident defense of biology (Science, 133: 1745-1748, 1961), surprised me more than a little bit. Since I do biophysics, I am not properly a biologist or a physicist, per se, but I do research that straddles the traditional boundaries of both fields. So I tend to look for good questions to be answered, and have not worried myself about whether my work is more "physics" or more "biology."

However, in his review, Mayr argues that there are questions dinstinctly biological in nature, and that these questions (along with some conceptual and methodological differences), make biology unique amongst the sciences. I thought I would paraphrase a few of the most interesting here:

Conceptual differences in biology

• The importance of historical narrative as an explanatory device.
• The prevalence of indeterminacy owing to the high frequency of stochastic processes, unknown factors, the presence of constraints, the interaction of multiple causes.
• The importance of quality (structure, form, function) in the properties and actions of objects, and a correlated reduction in the importance of purely quantitative differences.
• Presence of an historical constituent in the inherited program; hence legitimacy of "why" questions; capacity for the storage of historical information.

Methodological differences in biology

• The importance of observation in addition to experiment.
• The frequency of independent multiple solutions to the same problem.

Other autonomous aspects of biology

• All biological phenomena have two sets of causations, those controlled by the historically accumulated information of the genetic program (evolutionary or ultimate causations), and those controlled by the properties of the interacting system (proximate causations). The study of the historical components of each system is as legitimate a concern of biological science as the study of proximate causations.
• The outcome of biological processes is usually affected simultaneously by multiple causations, owing to the complexity of the systems interacting with complex biotic and physical environments
• Many properties of systems cannot be explained by a study of their isolated components.

It's interesting that many older biologists saw the successes of biochemistry and biophysics as a danger to the field of biology proper. Many early critics complained that such interdisciplinary research gave much to the other field, while returning relatively little to biology. In this light, the point about multiple causations (evolutionary and proximate) is still quite relevent, because the evolutionary causes are often unaddressed in many of the recent "hot" papers in biophysics.

Filed under biology · chemistry · physics · science

Posted by H. C. Hodges at 4:34 PM | Permalink | Comments (2)

Well, I read a rather surprising post from Derek Lowe today. Turns out, he thinks that most common buffer reagents are a bunch of hocus-pocus:

There's some reducing agent in there, naturally. Can't have those thiols turning into disulfides and balling up the protein, I understand - but does something bad happen if it's not in there? Generally, no one finds out, because, hey, why mess with it? And there's some EDTA, and some salt, and their function is? Well, as far as I can tell, they're also in there because they've sort of always been. Same goes for the squirt of detergent (Brij-35 or some such), and the tiny bit of bovine serum albumin, of all things. It's just part of the old-fashioned recipe from Grandma's Protein Kitchen.

Now, organic chemistry has a little of this, true, but it hasn't reached quite the Ancient Runestone levels of enzymology.

Lowe unexpectedly sounds like so many of the physicists I know that make snap judgments about how biology is done without the requisite background. As it turns out, many people do understand each reagent's use and shortcomings. We use many of those reagents for reasons that we understand pretty well:

1. Reducing agents protect methionines and cysteines from oxidation. If the protein is an intra-cellular protein, then this mimics the reducing environment of the cell. If there are structurally or functionally important cysteines on the protein, this prevents them from forming intra- or inter-molecular disulfide bridges. Generally, one doesn't want those, because they can lead to the protein becoming insoluble. You may also need them if you're going to do mass spectrometry, because you want to know the molecular weight of the monomers (not the disulfide-linked Nmers). Plus there are multiple types of reducing agents, and there are situations where you'd use one and not the other.
2. EDTA is in there because the researcher wants to prevent magnesium or other divalent cations from somehow affecting the molecule of interest. This "somehow" can include metalloprotease degradation or bacterial growth. Sometimes you have your own reasons for not wanting a protein to bind Mg²⁺ (like if an enzyme gains a certain reactivity upon binding). Also, magnesium is required by some nucleases, so the addition of EDTA can also prevent nucleases from degrading DNA or RNA, if those are present in solution.
3. Salt is just silly to question. Most proteins depend on salt for stability and solubility. Salt helps screen attractive and repulsive ionic interactions.
4. Depending on the protein, you may require the presence of detergents to make the molecule soluble. There are many different types of detergents, and you'd choose one (believe it or not) rationally, depending on the type of interaction you want with the protein. There are cationic, anionic, zwitterionic detergents, and polar (but uncharged) detergents too. These are especially important for hydrophobic proteins that would otherwise aggregate were detergent not present.
5. BSA may sound silly, but it's a stabilizing adjuvant. Not only does it tend to keep the test tube feeling like the cell by acting as a crowding agent, it also acts as a sink for protease degradation in the case that some contaminant makes it in the tube accidentally. In our lab, we use it regularly as a blocking agent to prevent nonspecific protein-protein interactions and protein-surface interactions. I imagine Lowe would be shocked to also find out that we use α-casein from milk for the same purpose. The reason we use these animal-derived proteins are because of their cost; they are also abundant, have no relevant enzymatic activity, and work well.

Thankfully, Lowe doesn't question the actual buffer itself, which is probably the most critical ingredient because it stabilizes pH. There are dozens of commonly used buffers, each one optimized for particular chemistries and with different pK_a values. For example, you might need a buffer without primary amines that buffers well at pH 8, in which case you may pick triethanolamine over the more common tris.

Each of these ingredients—even if one doesn't understand how it works—is often a required buffer component. These reagents are the moral equivalent of the glass flask in chemistry. Sure, I could deride Derek for using such stone-aged materials as "super-heated sand" for his Erlenmeyer flask, or "baked mud" for his Büchner funnel, but that would be silly and take a rather healthy amount of hubris. Instead, I recognize that these are the basic tools of chemists, and we move on.

In much the same way, these buffer reagents are some of the most basic tools in biology; they combine to provide a tightly controlled and consistent chemical microenvironment for proteins and other macromolecules.

Filed under biology · chemistry · science

Posted by H. C. Hodges at 8:05 AM | Permalink | Comments (0)

A lesson many scientists should learn:

Of course, the trick isn’t to "know it all," but to know what you don’t know. Or to be able to figure out what you don’t know, which is difficult, because you don’t know it all.

Since coming to graduate school, I've observed many condescending exchanges between people who often don't know the limits of their own knowledge. I think this "personality quirk" is more common amongst those who are good speakers—after all, it's easy to convince yourself that you're the smartest one in the room when those around you don't sound as eloquent as you do. So this got me to thinking, "how indicative is verbal communication skill of natural intelligence?"

I, for one, have a tendency to overvalue rhetoric proportional to its utility. I stumbled across this blog's archive that reminded me that it is too easy to confuse good speaking ability with intelligence:

I have often attributed, I think, too much value to eloquence. Somewhere along in my education, I mistakenly equated the ability to write and communicate fluently with the ability to think rationally. While they are not entirely separate, the one does not necessarily imply the other... Intelligence is not necessarily a prerequisite to eloquence, nor is eloquence necessarily an indicator of intelligence.

It's unfortunate that there are a great many students at top-tier graduate schools who have problems separating intelligence from good oral rhetoric. I think the ability to separate these two is of the greatest importance particularly for scientists, because we should always require good evidence and not be overwhelmed by masterful speaking.

Filed under culture · science

Posted by H. C. Hodges at 8:37 PM | Permalink | Comments (0)

This is pretty cool. Thanks, HHMI.

Filed under berkeley · biology · science

Posted by H. C. Hodges at 11:02 AM | Permalink | Comments (0)

Even though An Inconvenient Truth opens tomorrow in L.A. and New York, a lucky few of us here at Berkeley got an advanced screening of it tonight as part of the China - U.S. Climate Conference on campus. Al Gore was originally scheduled to speak in person, but sent an advanced copy of the film for us to see because he was unable to make it.

Although I haven't had time to fact-check, and I still need to let all the proverbial juices mellow, my first impression was "wow."

The movie was not so much a documentary in the style of Michael Moore, but rather, it was more like going to hear a very entertaining speaker. Gore is still goofy-doofus Dr. Namedropper, but once you learn to see past his not-terribly-likeable persona and actually listen to what he's saying (and realize that planet-wide changes are happening), it's pretty eye-opening. Even as a scientist, it's hard to pay attention to all the current geophysical research—I look through Science and Nature all the time where these articles are published, and it's overwhelming trying to piece it all together—nevertheless, Gore does a pretty good job of placing it all together into a good narrative... one that is very thought-provoking.

It's a powerful, powerful film, devoid of obvious hyperbole and I would recommend in a heartbeat for everyone I know to see it on opening weekend in your area. You can find out when and where it opens by going to the movie's website.

UPDATE: Man, Fox News is just out of control.

UPDATE: Grist blows away my review. Now, forget what you just read, and read this instead.

Filed under berkeley · culture · energy · science

Posted by H. C. Hodges at 10:12 PM | Permalink | Comments (0)

If you haven't already seen the ridiculous new pro-CO₂ ad campaign, then please click here. The Competitive Enterprise Institute (apparently an industry-funded lobby group) has made two new video ads to vilify the prevailing notion that global warming is bad.

The first time I saw these, I thought they were parodies... at least now we know how many content-less clichés one can put in a 60-second spot! Make sure you have speakers. Oh, and more fun at realclimate.org.

Filed under culture · energy · science

Posted by H. C. Hodges at 11:03 AM | Permalink | Comments (0)

This is one crazy optical illusion. Check it out! [from a labmate's boyfriend's website]

Filed under science

Posted by H. C. Hodges at 9:32 AM | Permalink | Comments (0)

You may have heard recently in the news about the patent dispute between Ariad Pharmaceuticals and Lilly. Ariad had licensed a patent from Harvard, MIT, and Whitehead that covers use of NF-κB activity. This patent (No. 6,410,516), created by David Baltimore and colleagues, claims much about the NF-κB system — there are a total of 203 claims in the Baltimore patent.

While a patent can claim virtually anything, the patent office's examination should help rule out claims that will not be upheld in court. However, in general there is no guarantee that patent claims will be upheld unless they conform to certain rules. In particular, in the US patent system, patents must be:

• A patentable invention: patentable inventions are any new and useful process, machine, manufacture or composition of matter, or any new and useful improvement thereof.
• Novel: in contrast to the rest of the world, US patents are granted to the first-to-invent, not the first-to-file. The patent will be ruled invalid if the invention:
  • was invented previously by someone else,
  • was described in a US patent application that is later granted with an earlier priority date, or
  • was known or used by others in the USA or described in a printed publication in any part of the world.
• Non-obvious: One must convince the patent office that the invention would not be "obvious" to someone else with similar knowledge at their disposal.

(from Patents for Chemicals, Pharmaceuticals and Biotechnology, 4^th Ed., Philip W. Grubb)

The claimed methods as described in the Baltimore patent are to me of questionable specificity. The researchers discovered a process of nature, then patented many of the obvious theoretically possible therapeutic routes dealing with that natural process. While US patent law is sometimes a little vague about the novelty criterion, it is generally accepted that processes or phenomena of nature can not be inventions, but methods which harness natural processes are fair game. So is it obvious, after discovering NF-κB's natural function, that one could inhibit its activity for therapeutic benefit? That's perhaps a more nuanced question than it first seems, so I'll let you decide.

From what I understand, Ariad is suing Lilly because Ariad claims Lilly's Evista and Xigris drugs modulate the activity of NF-κB. In its response to the case, Lilly asserted that they had "discovered these drugs and disclosed their medicinal properties years before the patentees' scientists made their discovery." At first blush, I'm inclined to agree with Lilly, but I certainly haven't heard all the details of the case.

I suspect the patent will not be upheld on appeal. As a matter of commerce, if Ariad were to continue winning in court, most pharmaceutical research would come to a halt. This is really a test case, because if Baltimore, et al, can in effect patent the entire NF-κB signalling cascade, entire companies will stop small-molecule R&D out of fear of patent infringement.

However, before the courts is not a matter of commerce, but a matter of law. Although normally I think I would root for the scientists and academics, I think this patent just might be overly broad...

UPDATE: I almost forgot that about two years ago, a friend of mine had the pleasure of meeting David Baltimore when he was giving a talk down at Stanford. She got to drive him around campus on a little golf cart to take him to various labs, and said he told some great stories... Incidentally, Baltimore is now the president of Caltech, and Giao has his (actual) signature on her diploma. Sheesh it's a small world.

UPDATE: See also my more recent post: "Ariad v. Lilly, revisited"

Filed under biology · patents · science

Posted by H. C. Hodges at 8:51 AM | Permalink | Comments (0)

Happy Cesar Chavez day to you all.

Right here is the Greatest Thing Ever about being a scientist:

Fig 1. This is the first time this event has ever been directly observed.

Right now, nobody in the world but me knows what this signal is. I'm the only person who has ever observed this event and knows how to make it happen again (although it happens in cells all the time!). Who woulda thought I'd finally get this project to work on a Cesar Chavez Day? Looks like I celebrated the holiday through hard work with minimal pay (which I think is most appropriate).

Filed under biology · science

Posted by H. C. Hodges at 9:14 PM | Permalink | Comments (1)

I've been reading the 4^th edition of Philip W. Grubb's Patents for Chemicals, Pharmaceuticals and Biotechnology, and so far, it's an excellent textbook. I would highly recommend it for those interested in the historical and philosophical developments of intellectual property rights in the biosciences.

This section on patents in developing countries caught my attention; I thought I would share an excerpt:

The entry into force of the TRIPs agreement in 1995 came at a time when the extent of the AIDS epidemic in Africa was becoming clear. Patented anti-retroviral drugs were being used in the USA and Europe to control the progression of the disease, but these drugs were very expensive and unaffordable for the vast majority of patients in developing countries. The perception arose, fostered by NGOs such as Médicins sans Frontières (MSF) and Oxfam, that patents were the reason why these drugs were not being made available to AIDS sufferers at an affordable price.

In fact, patents are not the problem. Not only are there no patents for most of these AIDS drugs in most African countries, there are also no patents in any countries for most of the drugs on the WHO Essential Drugs list—so why then are these essential drugs not readily available to patients in poor countries? The answer is simply lack of money to buy even cheap medicines, and lack of social and medical infrastructure to deliver them. The terrible truth is that if AIDS could be cured by a glass of clean water, there would still be millions who would have no access to the cure. Unfortunately, patents and the 'greedy' pharmaceutical companies make a much easier target than the miserly rich country governments and the corrupt poor country governments who together make up the real problem.

Despite the lecturing tone, Grubb succeeds in highlighting the asymmetric flow of criticism with regards to problems of the Third World. While it's common to hear that these problems stem from the actions of Wealthy Americans and Their Tool the WTO, we hear relatively little about the role of bad governance. Poor governance and lack of independent press consistently give rise to famine and abysmal social conditions (see: Zimbabwe), but few seem willing to confront this problem head-on. This brings to mind what I previously wrote regarding the whole Mohammed cartoon fiasco.

Grubb continues:

However, the pharmaceutical industry also did a lot of damage to its own image, notably by its legal action in the South African courts against the South African government over a proposed law for compulsory licensing of some pharmaceuticals. The proposed law was contrary to TRIPs and arguably unconstitutional, but the spectacle of the pharmaceutical industry suing Nelson Mandela (who was then still President, and was the first name on the list of defendants) in order to maintain control of drug supplies was a public relations disaster of the first magnitude.

Apparently, this debacle influenced the 2001 WTO meeting in Doha, as well as 2003 meeting in Cancun. This is quite an important story, because its outcome will affect how poor countries obtain access to pharmaceuticals. In particular, the result will decide whether poor countries obtain their drugs through legitimate or through illegal means.

One point of note is that if property rights for medicines were universally enforced, drug prices wouldn't be so high here in the U.S.A. Overseas manufacturers of cheap generics that infringe upon patents of pharma innovators are pirating intellectual property. Pharma piracy causes real damage to the actual innovators, because they lose out on income that would help recoup the cost of development; the result is higher drug prices for all and reduced investment in R&D.

In a global world, we are increasingly influenced by bad governance overseas. First World countries should be insisting on good government in the Third World. Unfortunately, the continuing legacy of colonialism makes things extraordinarily difficult.

Filed under culture · hiv · patents · science · textbooks

Posted by H. C. Hodges at 1:07 PM | Permalink | Comments (0)

Today, Irving Weissman gave the Marian Koshland seminar here at Berkeley. Weissman is the Director of the Institute of Stem Cell Biology and Regenerative Medicine at Stanford. He was also recently featured in The New York Times (see also here). The title of his talk was "Stem cells: Units of regeneration, units in cancer and units of natural selection." He's a pioneer in the science of stem cells (having isolated and characterized the differentiation of the blood-forming cells); he also gives an awesome talk.

He started with an introduction to stem cells, then discussed how stem cells have been implicated in acute myeloid leukemias. His aim is to understand why 2-3% of tumor cells have properties similar to self-regenerating stem cells, and from all appearances, he is making progress. By regulating the expression profiles of hematopoeitic stem- and progenitor-cells, his lab is able to precisely control and induce cancers in a controlled way, including regulating the proliferation of monocytes from chronic myelomonocytic leukemia to