Cancer Therapeutics

Nature discusses the new drug from Moderna and Merck for treating advanced melanoma. They note:

A personalized mRNA vaccine reduced the risk of skin cancer returning or the recipient dying by 42% when used alongside an immunotherapy drug, according to long-awaited results for what could become the first approved mRNA vaccine for cancer. Oncologists regard a risk reduction of 10% as substantial, says Kristen Radford, an immunotherapist at Mater Research in Brisbane. A more than 40% risk reduction “would send many researchers over the Moon”, adds Seth Cheetham, a geneticist at the University of Queensland in Brisbane, Australia. The personalized vaccine, called intismeran, is not designed to prevent skin cancer, or melanoma, from developing in the first place, but to stop it returning in people who have already undergone surgery to remove tumours.

 As shown in the graphic, this is one of the personalized approaches. Simply the approach is as follows:

1. Get a sample of the tumor from the patient.

2. Sequence the DNA and determine what unique cancer mutations may be there.

 3. Generate a mRNA using these mutations.

4. Place the mRNA in a package, such as a liposome, and inject in patient.

5. mRNA will generate these related protein, many of which produce cello surface targets.

6. The patients immune system will see these as antigens and attack cells with these Ag surface targets

7. Add a PD-1 blocker which insures that the immune system remains on and not turned off

8. Pray the immune system works on the cells targeted and does not explode on everything else.

Now the key here is personalizing the surface proteins. In reality if we can do this for many patients then we can get a reference set, and the identity of the correct one may be more easily done by antibody tests. Say a patient comes in, we have this database of targets based upon many prior patients. We can then have Ab targeted for each one of the gene mutations and can then simple use Abs targeted for them. From this we get in no time the mRNA profile, generate it, put in liposome and voila! Kind of.

In reality we must always be concerned about immune system over response, such as cytokine storms. I fell the full story is yet to unfold. One must remember CAR-T cell promises.

I have noted a similar approach but using antibody drug conjugates, ADCs. It requires a database of surface targets on cancer cells, and then generates polyspecific Ab with a conjugated drug.  

But, and this is important, many cancers are "protected" by a tumor micro environment, TME, and one must break through that as well. 

 

The Collapse of the University

 One wonders who is behind these actions. The Tech at MIT notes:

 Out of 1,708 ballots, 92.5% of members of MIT’s Graduate Student Union (GSU) voted yes to authorize a strike yesterday evening. During a strike, graduate workers and fellows would be expected to stop all work and “not cross the picket line.”  After six months of bargaining and 15 sessions with MIT, seven articles (5, 7, 10, 13, 14, 19, and 25) have reached a tentative agreement, while the majority remains in limbo or has been closed. However, central issues to the GSU’s campaign — union shop, establishing a three-year contract, wages, healthcare, and protections for international workers — remain at a standstill with the Institute.

 So let me try to get this correct. A Grad student will refuse to work on their thesis or perform Teaching Assistant duties to undergrads who are paying nearly $100,000 per year! 

This may very well  be the start of the collapse of the University system. Who are these people who are behind this. We have teachers unions who have been able to destroy Grammar and High Schools in the US while union leaders collect millions. 

This strike is a great way for some adversary to destroy US academic excellence. Remember that nothing is necessarily what it appears to be. In this case it may very well not be some "poor" grad students. 

And This is Science?

 

I was amazed by the interview in the NY Times of the so-called science advisor to the President. This person, a BA from Princeton in Poly Sci, not any apparent technical expertise, notes:

S.I. for science is going to be the biggest unlock for scientific discovery in the history of the world. It’s going to impact everything from material science to chemistry to math. In our plan, I think the belly button of it all is something called the Genesis Mission, the idea that we should build a scientific instrument in the federal government to be able to leverage S.I. for scientific discovery, and that’s what we’re building in our national labs. And we’ve opened it up, and now have access to it, from all of our agencies across the government. So if you’re doing very important health care work or biomedical work that requires superintelligence, you can access this instrument at the D.O.E., and the same goes for lots of other agencies. The core thing we want to do is provide S.I. as an enabling tool for whatever scientific discovery you want to make.

Great, just what we need, more Government Labs building stuff!

I had the good fortune to have known three Presidential Science Advisors: Vannevar Bush, Jerome Wiesner, and EE David. In my opinion this is not one of them. But I continue:

 So right now, American Ph.D. programs are geared toward this, at a minimum, five-year Ph.D. But they’re also tailored to try to optimize the curriculums in order to train students to be academics, and the numbers don’t play out. About 60 percent of people who get Ph.D.s do not end up becoming academics. So we asked ourselves: In that environment, shouldn’t we be trying to do a better job of training these young technologists and scientists to go out and actually be prepared for what they’re ultimately going to do in industry? So we launched a four-year Ph.D. program in partnership with universities and with industry, so that during the last year of your Ph.D. program — at year four — you’re at an industry lab. You do work in industry, and your dissertation is written on the work that you do at that company.

 This is a work study program, not a research training exercise. Now to be simple, my PhD took 18 months. I had an SM from MIT already and needed a few extra courses, but I stuffed it all in. I also was a junior faculty member as well as finishing my first book. Plus a few other things along with two children. I never could have done that in some work study program. 

With my MIT PhD I ran the gamut of academic, Government Advisor, Movie and CATV business, COO of mobile phone business, venture investor and operator, etc. The PhD allowed versatility and MIT, at the time (and that was during the Viet Nam War folks) allowed me to explore. 

The current so-called Science Advisor seems to follow the path of using neologisms to espouse new policies. PhDs are not "trained". They are educated and tested. You may "train" your poodle but please let's not insult the Academy, it already has a multitude of problems.  

Would it not have been better to have an experienced PhD in this position, say in Science or worse case Engineering like the three I have known! Instead we get an apparently inexperienced political entity.

Funding Science

 

In a short piece in Nature the authors discuss the increase in private funding or research, especially in the biotech arena. They note:

 

And US tech entrepreneurs have a penchant for experimentation in how they structure their investments, says Keith Yamamoto, vice-chancellor of science policy and strategy at the University of California, San Francisco. When it comes to philanthropy, private donors are more able to take risks with their investments than are government funding agencies, which are beholden to taxpayers to ensure that their money is spent wisely. “Public money limits your activities,” says Harold Varmus, a former director of the NIH, who has also been on advisory boards for the Gates Foundation and the CZI. “There is a freedom of motion that is associated with private money.” Some tech titans have experimented with various ways of structuring their grants. The Arc Institute, for example, boasts a “no-strings-attached” funding system that gives its investigators more freedom than do standard government grants awarded to biomedical researchers. Philanthropists are also able to fund long-term, interdisciplinary projects that can be difficult for government grants to take on. Convergent Research, a non-profit organization funded in part by Eric Schmidt, the former chief executive of Google, is forming ‘focused research organizations’ that bring teams together to solve important scientific or engineering challenges that could benefit a wide swathe of research. “We’re looking for the pieces of critical, fundamental infrastructure missing from a particular field,” says Anastasia Gamick, a co-founder and president of Convergent Research, which is headquartered in Cambridge, Massachusetts.

 Targeting research is a difficult process. One of my favorite targets was Multimedia Communications, now embodied in the current Internet world. But then many in management had no clue. A phone call was enough. Thus a good researcher will go for long term high impact work whereas the funders may have conflicting ideas. It should be interesting to see how this evolves.

 

 

Business Schools

 First let me state I have no MBA. In fact I had just one course in economics as a undergrad. But I spent a year at Columbia as a visiting Professor at the Business School and a couple of years at NYU/Poly. Now how did that happen?

Simple, I think. In the late 70s at  I was at COMSAT and Gene Jilg, a VP of Satellite Systems, asked me to write his business plan. Never did one. Especially the financials. So one Friday I went to a local bookstore and bought a book on Finance. Read it over the weekend and on Monday I started the financials. You see as an MIT EE PhD these were just simple equations and I just asked around for the data. Done in a few weeks. 

At Warner I had plans for  interactive video, managing a staff of a few dozens, marketing, tech, valuation. Then deals. Again not a single business school class. 

The NY Times notes:

The modern business school is designed to promote dealmaking, simplification and optimization. This mind-set has escaped containment and has spread to the wider world. Business-educated elites increasingly populate political leadership, bringing with them a transactional view of public life. One investigation found that out of 45 current heads of state who had studied in the United States, 10 were business majors, and six of those also earned M.B.A.s. President Trump, a Wharton undergraduate, has treated foreign policy and government itself as extensions of deal making and personal gain. Surely, not every business graduate governs this way. But recent research by the Nobel laureate economist Daron Acemoglu and colleagues shows what tends to happen when you put an M.B.A. in charge. In both the United States and Denmark, firms that appointed managers with business degrees cut wages and reduced labor’s share of income. Yet these companies didn’t become more productive, nor did they grow sales, investment or employment any faster. What registers as managerial acumen turns out to be wealth transfer — value moved away from workers and toward profits, shareholders and executives.

 In contrast I have seen High School Grads in retail have a better understanding of the customer, inventory, and turnover than many a B School grad. I gained more insight by doing than by studying. It was getting in the line of fire and surviving. The most complex one is selling a new business. One has to be a dream merchant of sorts, and then defend your proposed valuation. I do not think you get that in class. 

It is a bit like Med School. Two years of "theory" then two years of real people, death, fear, mistakes, and cures. There are no pre-cooked case studies. There is a 2AM ER case of a 65 year old mother and her 38 year old daughter, her pain but more so her fear. It is the 12 year old with Leukemia and you must tell the parents, see their horror about their child. Creighton wrote a great book, 12 Patients, his last two year at Harvard. It was not academic class, it was life and death. There is nothing like that in B School. 

Thus one wonders if B School has value.  

Unionized Grad Students

 

The MIT Tech discusses the Graduate Students Union. They note:

Since April, MIT’s bargaining team and its graduate student union (GSU) have held multiple meetings to negotiate a second collective bargaining agreement, reaching tentative agreement on three of 26 proposed articles. The original contract expired on May 31, leaving around 5,000 graduate research assistants, teaching assistants, and Instructor-Gs working under the terms of the expired agreement. After months of stagnant bargaining, the GSU launched a pledge on September 9 to strike if necessary. In a press release dated Sept. 11, 2026, the union announced that over 1,000 graduate workers have signed. It is not clear when exactly the GSU is planning to strike, but the last bargaining session in the month is planned for September 25.

Now back in my day, mid 60s, you never would have time for this.We were all to busy on our research. We all got the same salary, $400 per month, plus MIT Health Service. You survived, barely and worked 24 by 7! If you were lucky, as a junior faculty, you got a day a week for outside consulting, and that could be $125 a day. You could double your salary. But it still was 24 by 7!

More than half of these folks are foreign students, getting free tuition, and almost $5,000 per month! Plus they want full health care. Many may need complex medical care, costly as well.

Just the site of this massive group, in my opinion, of proto-Marxists, is terrifying (namely the appear to be class oriented, Grad Students vs the Institute). So do we have a problem with higher education, you betcha! 

But the bottom line in the "old days" was that you tried to be better, more creative, ahead of the crowd. The last thing you sought was group compliance.  Frankly you tried not to be equal as a group. You tried to be better as an individual. Unions, as I have experienced, are possibly good if the class of people are doing the same task. Say a bus driver, chicken plucker, garbage collector. But an MIT Grad student is doing a one of a kind, research, pushing the frontier forward.